DE1445518A1 - Process for the preparation of new halogenallylpiperidines - Google Patents

Description

DR. F. ZUMSTEIN - DR. E. Α88ΜΑΝΝ - DR. R. KOENIQSBERQER PATENT LAWYERS

β MDNOHEN »,

TELEGRAMS: CUMPAT BRXUHAU8STRA8SE 4 / m CHECK ACCOUNT: MÖNCHEN Oll

BANK ACCOUNT: BANK H. AUFHXUSER

DW / fro

Gases 1/732 (176)

C. H. Ου Ehr ing he son, Xngelheiai am Rhein,

Process for the production of new Halogenallylpiperidir-βη

Ee it was found that Pipevidinderivata of the general formula

R ₁ K

r.

80981 1/1085

'. HCl

mm

1- (3-chloroallyl) -4-2-methylphenyl) -4-propionyl-piperidine hydrochloride 2.7 g

4- (2-methylphenyl) -4-propionyl-piperidine hydrochloride

+ 1.3 g 1,3-dichloropropene- (2)

"BeTspT

2.0 g 58 *

l - (> chlorallyl) -4 (3-methylphenyl) -4 acetyl-piperidine hydrochloride 2.65 g

4r U-methylphenyl) -4-acetyl-piperidine hydrochloride

+ 1.3 g 1,3-Di chiorprop * n- (2)

2.2 g 67 *

i - (> Chlöraiiyi} -4- 2.8 g

k- (2-methylphenyl> -4

11.5

2.0 g -

y din-hjrdro chlorld

■■ + ■ "j ' ι τ T""

1,3'DiChIUi ^ r αφ «* - (2)

14A5518

80981 1/1065

trana-1 - (3-chloral Iy] 4- (3-methylphenyl) -4-iaethoxycarbonyl-piperidine hydrochloride

chem. Designation

. "I atiulftur formula

l-O-chlorallyl) -4-

(5-methylphenyl) -V

4-methoxycarbonyl-

plperidin hydrochloride

Starting material?

2.8 g

4- (2-methylphenyl) -

4-methoxycarbonyl-pi-

perldin hydrochloride

+ 1.3 g 1,3-dichloropropene- (2)

cia-1- (3-chloroallyl) - Τ- (2-raethy1phenyl) -4-ethoxycarbonyl-pipe- -ridia-hydrechlorid-.

2.85 g

Ü- (2-methylphenyl) -4 ethoxycarbonyl piperidine hydrochloride

+ 1.2 g

trans-1,3-dichloropropene- (2)

2.85 g

4- (2-methylphenyl) -4-

ethoxycarbonyl-piperi-

dih hydrochloride

+ 1.3 g

cis-1,3-dichloropropene- (2)

IV

COCH,

. . ·. HCl

yH.

(4-methylphenyl) -. Acetyl-piperldine hydrochloride

. . 2.65 g

4- {4-methylphenyl) - · 4-acetyl-piperidine hydrochloric! ....

+ l,> g ... 1,3-dichloropropene- (2)

■ 7: .-

'225 · · -

Q <
• ζ-

(3y) (4-methylphenyl) -4-propionyl-piperidine hydrochloride 2.7 g

4- (4-methylphenyl) -4-propionyl-piperidine hydrochloride .

+ 1.3 g
1,3-dichloropropene- (2)

1.8.g =.

16

OCH ₁

- (3-Chlorallyl) -4- -methylphenyl) -4-methoxycarbonitl-piperidln-hydrochloride

g - CH --- C '

HCl

H
Cl

• 2.75 g

M4-methylphenyl) -4-methoxycarbonyl-piperi din hydrochloride

. + 1.3 S.

1,3-dichloropropene (2)

2.1 g 61%

201 203

►

! it :.

Structural formula

former designation

Starting material

analot fteisp.

Time (Hours.)

Yield

V (3Chloy

(^ -methylphenyl) -4-

ethexycarbonyl-piperl

din hydrochloride

2.8 g

4- (4, -Methyl phenyl) -4-

Hthoxycarbonyl-piperi-

din hydrochloride

. 1.3 g

1,3-dichloropropene (2)

1 * 8 g

19 * - Γ97

l- (3-chloroallyl) -4 - (; 5, ^ - dimethyl phenyl) - ^ -propionyl-piperidine hydrochloride

HCl

2.7 g

* - (3, * - Dimethylpheny1)

^ -Propionyl-plperi-

din-hydrochlorld

t 1.3 κ 1,3-chloropropene- (2)

l CH ₂ - CH

227 -

CK ₁

- (3-chlorallyl) - * -

2.9 β

^ -niethxycarbonyl- ■ piperldine-hydrochlprldj

(3, yp nyi) -4-methoxycarbony piperidine hydrochloride

♦ 1 * 3 g 1,3-dichloropropene- (2)

204 205

- \ Aw ^ tzgääS

/ t he ^ η

I ^ CH, -Cl (3, ^ - dimethylphenyl) - trar.s- 3.0 ε 1 I. I. -1.1 K 1 7th 2.2 g = 236 - J I. fc-Hthoxycarbonyl) -pi- l -;. 3-chloroallyl; - ^ - ⁱ <- (3, ^ - dimethylphenyl) tran £ -1, J-Dinhlcr- 595 < 238 I "ι ο peridln hydrochloride (2-chlorpher.yl) - ^ ^ - ^ thoxycarbcnyl-pi- prcpen- (2) ^ <^ ^C -OC ₂ H ₅ propicnyl-piperldine- perldln-hydrochlorld 2.9 ε IJ · HCl hydrochlorld 1,3 - Ilcrpropenr [2) "-1" -Chiorpheriyl,) - IH
CH _D - CH * C ^ _r , --Lropicnyi-piperi- trans-l- (3-ChlcraiIyI) t.8 g din-iiydrochlcrld Ii η- (2- «hi orphenyl) - ^ - 80981 1/1065 ■ ^J1 - {2-chlorophenyl J- · '· - ';: ^{? G} }, 2 g - 192 - 8th'
< x ^^ i - Cl «Icety l-piperidine-hy- aoetyl-piperidine-hy- ^ <T ^ COCH, drocihlorld drcchicrid 193 1] · HCi 21 Tr CK ₂ - CH. < _C1 7th 1.2 g - 2 ι 7 - | j " 2 B v3 * C *. KJ ^ C ^ rCOCpH ^ O 144551 cc. I.

Structural formula

CCCH,

CH ₂ - CH

= C.

HCl .H -Cl

chemical name

1- (3-chloroallyl) -4- (3-chlorophenyl) -4-acetyl-piperidine hydrochloride

Source material

2.8 g of 4- (3-chlorophenyl) -4-acetyl-piperidine hydrochloride

♦ 1.3 g
, 3-chloropropene- (2)

analogue
BeisD.

Time
(Hours.)

Yield,

1.9 ε. »

55 *

192 193

COC ₂ H

C ^ y) (3-chlorophenyl) -4-propionyl-piperidine hydrochloride

. HCl

2.9 g

4- (3-chlorophenyl) -4-propionyl-piperidine hydrochloride

ti, 3 g
1,3-chloropropene- (2)

1.8 g = 50%

CH ₂ - CH

238 239

—OUCH,

1- (3-chloroallyl) -4- (3-chlorophenyl) -4-methoxycarbonyl-plperidine hydrochloride

HCl H Cl

2.9 g

h- (3-Chlorophenyl) -4-methoxycarbonyl-piperldine hydrochloride

4.1.3 s

1,3-dichloropropene (2)

8098) 1

1.8 g " 49 *

195 197

Structural formula Source material

Ex.

(Hours.)

1- (3-chloroallyl) -4- (3-chlorophenyl) -4-ethoxycarbonyl-piperidine hydrochloride

3.1 g

Sthoxycarbonyl-pip - ridin hydrochloride

, 3-dichloroprop "n- (2)

1.9 g 50 *

211 213

l- (3-chloroallyl) - * -

2.8 g

, CCCK,

acetyl-piperldine hydrochloride

acetyl-piperldine hydrochloride

- 1.3 g 1,3-chloropropene- (2)

- cn -

1.9 g -

198 200

2.9 g

COC ₂ H ₅

1- (3-chloroallyl) -i »~ (4-chlorophenyl) ^-1 » - proplonyl-piperidihhydrochloride.

Hfl

'■ ^QH - ^ ci

proplonyl plperldine hydrochloride

t 1.3 gl, 3-dichloropropene- (2)

809811/1065

1 * 5 g

41 *

225 226

No structural formula

former designation starting material. .al

analogous to Beiep.

Time- (hrs.)

yield

2.9 g

OCH,

1-O-chlorallylM - (^ - chlorphenyl) -4 methoxycarbonyl-piper idin hydrochloride

HCl

mefchoxycarbonyl piperidine hydrochloride

-1.5 g
, 3-dichloropropene (2)

CH ₂ - CH - C.

"Cl

2.0 g 555 "

199 200

OC ₂ H ^

* HC]

«C

l- (3-chloroallyl) -4-

ethoxycarbonyl piperidine hydrochloride.

ethoxycarbonyl piperidine hydrochloride

* 1.3 S.
1 ,, 3-dichloropropene- (2)

2.1 g = 55 *

1- (3-ChI oralIyIM- (J ^ 'faultorphenyr) - ^

C H ₃ - CH

HCl

propionyl piperidine hydrochloride 3.25 g

(3, lpy 4-propionyl-piperidine hydrochloride

1.3 g
1,3-dichloropropene (2)

1.8 g

Belsp.

l- (3-chloroallylM- (3,4-dichlorophenyl) -

4-methoxycarbonylpiperidine hydrochloride 3.3 g

Ji- (314-dichlorophenyl) · h -methoxycarbonyl-piperidine hydrochloride

♦ 1.3 g
1,3-dichloropropene (2)

1- (3-chloroallyl) -4- (3,4-dichlorophenyl) -4-ethoxycarbonyl-piperidine hydrochloride

HCl

3.4 g

4- (3,4-dichlorophenyl)

4-ethoxycarbonyl-piperidine hydrochloride

* 1.3 g
1,3-dichloropropene (2)

CH ₂ - CH -

l - (> - chlorallyl) -

M2,4-dichlorophenyl) 'i-propionyl-piperi-

din-hydrochlca ^ ld

HCl

- CH = Ci

.H
Cl

3.25 g

4- (2,4-dichlorophenyl) ■ 4-propionyl-piperidine hydrochloride

* .1.3 g
1,3-dichloropropene (2)

RP 9 R 1 1/106 5

2.2 g

552

2.1 g =

199 201

223 -ι

225 ^ a

207 209

1445511

Structural formula

former "^ drawing

Exit mat IaI

analogous to example

2.9 g

. HCl

CH-- -C = CH ^ -

chlorophenylM-methoxy- ₄ - (3-chlorophenyl> 4-carbonyl-piperidinemethoxycarbonyl-pi-

hydrochloride oeridine hydrochloride

CH ₃

COCH,

. HBr

1- (2-3romallyl) -4- (2-methylphenyl) -4-acetyl-plperidine hydrobromide

. ^ = CH

H,

COCH,

1- (2-Bromoally.1) -4 (3-methylphenyl) acetyl piperidine hydrobromide

H3r

.- C -

M ₁ Dg

-3rom-2-chloropropene- (2)

2.65 g

4- (2-mechylphenyl) -4-

acetyl piperidine hydrochloride

⁺ 2.2 g
1,2-Dlbromopropene (2)

2.65 S

4- (3-ttfchylphy)

acetyl piperidine hydrochloride

⁺ 2.2 g
1,2-dibromopropene (2)

/ λ λ r- If

Time (hours)

yield

2.5

2.5

ο C

14455

HCl

HCl

CH ₂ - C = CH ₂

Br

COCH,

HBr

- C = CH ₂

Br

1- (2-Bromoallyl) -A- (3-methylphenyl) ^-1 * - methoxycarbonyl-piperidine hydrochloride

2.75 g

^ - (3-Methylphenyl) ^-1 ^ -methoxycarbonylpj peridine hydrochloride

► 2.2 g
1,2-dibromopropene (2)

ex.

1 - (2-bromoal IyI; -4 (3-methylphenyl) -A-

ethoxycarbonyl-piper'idln-hydrochl prid

2.6 g.

A-OMethylphenyl ') - ^ -äthcxycarbcnyl-piperidinhy.drcchlorid

t 2.2 g. 1,2-rDi bromopropene (2)

l- (2-bromoallylM- (4-

methylphenyl-4-acetyl-

piperidine hydrobromide

2.65 g

4- (4-methylphenyl) -4-acetyl-piperidine hydrochloride

f 2.2 g
1,2-dibromopropene (2)

j ι

2.5

j 3.1 g
• 80 *

2.5

2.5

3.9 g =

3.5 g

203 2C4

177 178

229 231

. 14455

8 ο

CH, ahem. designation ! ■ Exit with trial .-. "■ ' + 2.2 g analOf ■ ZtIt
(Hours.) yield ⁰ C ν
f # i-i? -Bro.T, allyl) -4- ^ • 75 p 1,2-dibroinpropene (2) 'j 206 ^ i (3-chlorophenyl) - * ^ * - (^ -Methylphenyl) - • 1 . - 208 ^ · 1- (2-BrOKaIIyI) -A- methoxyoarbonyl-pi- ^ - ■ ethoxycarbonyl- j » ^> ^ **** OCH ί ^ -raethylphenyl) - ^ - peridin hydrochloride piperldine-hydro-
chlorld 1 2.5 3.0 g - 215 - ι tre thoxy c arbony 1- pi » "■ * r (^ -Chlorophenyl) - ^ - 69X 217 / J 'KEr peridin-hydrobrcirid methxysarbonyl-pi- «- ■■■ 2.2 β peridin-hydrcchlorld W. CH ₂ -C-CH ₂
He. - 1 , 2-dibroapropene (2) M. Cl · «■ 2.2 g .. ' · • Ir 2.6 β
^ -OCchlorophenyl ) -k- 1,2-di-bromopropene (2) 193 - V ^ COCH, l- (P-bromoallyl) -4- acetyl piperidine 195 Born (Ji-chlprpheiiyl} -4? hydrochloride 1 2.5 J m. O IT ¹ pc r- 42 £ J "HBr acetyl piperidine QaV '. hydrobromide I.
CH ₀ -C- CH "
ί Br Cl 2.5 98 ^ / j · HCl j I.

Cl

COC ₂ H ₅

* HCl

C-CH ₂ Br

(4-chlorophenyl) -4-

propionyl piperidine

hydrochloride

2.9 β

prop! onyl-piperidine hydrochloride

2 _f 2 g

2.5

2.9 g 71Ji

217-219

Cl

i- (2-bron> allyl) - * -

(4-chlorophenyl) -'.-raethoxycarbcny1-piperidine hydrochloride

HCl

2.9 g

4- (4-chlorptaeayl) -4- methoxycarbonyl-pi- peridin-hydrochlorld

t 2.2 β

1,2-dibrorapropene ( 2 )

2.5

-C-CH

^209-1210

COCH,

kc:

1- (3,3-DlChIOrEiIyI) -A- (3-methylphenyl) -4-acetyl-piperldine hydrochloride

- C; i .. C '

2.65 g

t- (3-methylphenyl ) -4- acetyl-piperidine hydrochloride

+ 2.C g

1,3,3-trichloropropene- (2)

80981 1/1065

3.0 g -

83 *

235 238

No. BATH - 49 3 STRUCTURAL FORMULA former designation Starting material ^ aI 2.9 g analogue
Ex. 1 Time
(Stud) 3 yield I. 3g = Fp
⁰ C O 8 2.75 g 4- (3-chlorophenyl) -4- MM \ J ^ v / CH ^ 4- (3-methylphenyl) -4- methoxycarbonyl-pi- l- (3,3-dichloroallyl) - methoxycarbonyl-pi- peridin-hydrobronr.id 4- (3-methylphenyl) - peridine hydrochloride 1 3 3.7 g = 218 - 47 ^^ ^υ -OCH, 4-methoxycarbonyl- + 3.1 g 9835 219 Yy piperidine-hydro- + 2, upper floor 1,3,3-tribromopropene- (2 Ll · HCi chloride 1,3,3-trichloropro- * pen- (2) I .ei 4.9 g CH ₀ - CH = C ^ 92J6 2.9 g 4- (3-chlorophenyl) -4- ^, ^ Cl l- (3,3-dichloroallyl) - methoxycarboayl-pipe- 224 t 4- (3-chlorophenyl) -4- ridine hydrochloride 1 3 ^ ς4 δ *; fj methoxycarbonyl-pl- 4th ^^ ^ OCH, peridine hydrochloride + 2.0 g Yy 1.3.3-trichloropro- I. V | ^ * HCl
I .ci pen- (2) C; • C. Cl l- (3,3-dibrorr, allyl) - 23Ο - 4- (3-chlorophenyl) -4- 232 ^ sL * "^^ OCH methoxycarbonyl-pipe- ridm hydrobromide Il · HBr CH ₀ - CH = C

03
α ο ^ V Cl l- (2,3-dichlorailyl) -
4- (3-chlorophenyl) -i-
methoxycarbonyl-plpe-
ridln hydrochloride 2.9 g
4- (3-chlorophenyl) -A-
methxycarbonyl-pi-
peridin hydrobromide
+ 2, Ig Eelsp. 'Tstci.)' 3.6 g - 1 ft - Γ *
51 V _- J * HCl
CH ₀ -C = C
CJ> ^ TJ
I π
Cl 1,2,3-trichloropropene
(2) i ■ farfiamm, ■
° c 4th
i 5C \ fJ · HCl l- (3-chloroallyl) -4-
(3-hydroxyphenyl) -4-
propionyl piperidine
hydrochloride 2.33 g
A- (^ -hydroxyphenyl) -
A-prcpionyl-piperi
din
1,3-dichloropropene (2) 1.8 g - 221 -
222 52 CH ₂ -CH- CHCl 2 2 214 1- (3-chloroallyl) -4-.
(3-hydroxyphenyl) -4- ■
butyryl piperidine
hydrochloride 2.47 g
A- (3-hydroxyphenyl) -4-
butyryl piperidine
+ 1.23 g
1,3-dichloropropene- (2) 2.1 S - CO ¹ I.
CH ₂ -CH- CHCl 2 2 80901 1/1065 14455

Structural formula

chera. designation

Source materialJ.

analogous to example

Tent (hours)

Expanded

(3-hydroxyphenyl) -4-

propoxycarbonyl-plpe-

ridln hydrochloride 2.99 β

4- (3-hydroxyphenyl) -4 < propoxycarbonyl piperidine hydrochloride

+ 1 # 23 g 1,3-diochloropropene (2)

1- (3-chloroallyl) -4 - (- 3-roethoxypheny 1) -4 propionyl-plperidin hydrochloride

2.47 g

4 - (3-methoxyphenyl) -4-propionyl-piperidine

HCi

CH ₂ - CH - CHCl

61 ,!

'2 ⁿ 5

i- (3-chloroallyl) -4- (3-methoxyphenyl) -4-ethoxycarbonyl-piperidine-hydrochloride

HCl

CH ₂ - CH - CHCl

Hours T ~ T

T ^ v

WbA UAIiUi 4. Ul'IUCX

cnero.-ceiexonnung rtusgangsinaieritii

Belsp,

Hours. )

trans-

1- (3-ChlorallylM-O-acetoxyphenyl) - ^ - raethoxycarbonyl-piperidine hydrochloride * », 5 ß
l- (3-chloroallyl) -4-

(3-hydroxyphenyl) -4-methoxycarbonyl-piperidine hydrochloride

+ 5.0 ml acetic anhydride

S =

CH ₂ - CH »CH Cl

* HCl

1- (3-chloroallyl) -4- (2-hydroxyphenyl) -4-methoxycarbonyl-piperidine hydrochloride 2.71 g

A - ( 2 - hydroxyphenyl) - ^ -methoxycarbonylpiperidine hydrochloride

+ 1.23 g 1,3-dichloropropene- (2)

CH ₂ -CH- CHCl

l-O-chlorallylM- (4-hydroxyphenyl) -4-

methoxy carbonyl pi. peridine hydrochloride

HCl

- CH ■ - CHCl

2.71 g

4- (h -hydroxyphenyl) - ^ -methoxycarbonyl-piperidine hydrochloride

+ 1.23 g 1,3-dichloropropene- (2)

80981 1/1065

2.0 g =

2.6 g =

144551

* t * Structural formula chem designation Source material 1 analogue
Ex. ■ 4th time
(Hours.) 2 2 yield Pp I
⁰ C 154 -
158 GH ΖΛ7 c oc- oi - 3-methyl - * - (3-hydroxy- • I 7 .o l- (3-Chloraaiyi) -3- ^ nenyi ^ - ^ - propicnyL- 2 2 '»Fas» 107 ^^ ^c ^ c H raethyl - ^ - C-hydroxy- piperidine ^ \. "^ 2 5 phenyD - ^ - propionyl- ι ι ^CH 5 piperidine-hydro- + 1.25 g oC-> | ^ · HCl chloride i, 3-Lichlororcpen- (2) . 3 Shape . "■ 'CH ₂ - CH» CHCl c £ ice cream 2.60 g oC- l- (3-chlorallyi) -i- 3-methyl- h- [ 3-hydroxy- ^^^ "^^^" OCH raethyl-4- (3-hydroxy- phenyü - "- methcxycar- ^r ~ _t -Q phenylJ - ^ - methcxyear- bonyi-piperidine- 2.0 g = 125 - Γ> —CH ^ bonyl-piperidln-hydro- hydrochlcrid 128 ^ \ \ ^ · HCi chloride + 1.23 g cis- I.
CH ₂ - CH - CHCl.
et · ™ i, ^ - Lichloropropene- (2) I. shape 2.85 g ^, ^ OH oL - trans vC -3-methyl-iJ- (3-hy- 61 ^^ \ ^ ⁰ ^ OCH, l- (3-chlorajlyi) -3-
methyl-4- (3-hydroxy-
phenyl) -4-methoxy carbc droxyphenyl) -4-meth-
oxycarbonyl-piperi-
_iyl _ din-hydroehlorid 2.3 ε » piperidine hydrochloride + 1.23 g trana- I. 1,3-dichloropropene (2) O ₆ - CH ₂ - CH = CHCl

- CH = CHCL

β - Lrans -

- O-chlorallyl) .- 3-methyl - ^ - (5-hydroxyphenyl) - ^ - methoxycartonyl-plperidine hydrochloride

2.85 p

fi-> methyl-4- (3-hydroxyphenyi) -4-methoxyoarLcnyl-piperidine-hydrochloride

+ 1.2.5 Β

trans-i, 3-dichloropropene- (2)

■ 5wr4

g =

1 DO -

OCH

* HCl

ß - ice -

l - (> ChloraLlyl) -3-nr.ethyl - ^ - CJ-hydroxyphenyl) -4-methoxycarbonyl-piperIdine hydrochloride

CH ₂ - CH * CHCl

β-3-Kethyl-4- (3-hydroxyphenyl) -4-methoxy-carbonyl-plperidin-hydrochloride

+ 1.23 g cis-l ^ -dichloropropene- (2)

2, C 55.5

50 -55

64

HCl

1- (2-Chloroaliyl) -4- (3-hydroxyphenyl) -4-acetyl-piperidine hydrochloride

. c = CH

4- (3-hydroxyphenyl) acetyl piperidine

+ i.23 g

2,3-dichloro-l-prc- pen

809811/1065

2.6 g - '

185

Structural formula

former designation output file_a1

analogous to example

Time (hours)

yield

1- (2-chloroallyl) -4- (3-hydroxyphenyl) -4-propionyl-piperidine hydrochloride

HCl

2.33 g

4- (3-hydroxyphenyl) -4-propionyl-piperidine

+ 1.23 g of 2,3-dichloro-1-propene

CH ₂ -C

2.4 g

CCH,

HCl

1- (2-chloroallyl) -4- (3-hydroxyphenyl) -4-methoxycarbonyl-piperidine hydrochloride 2.71 g

4 - (3-hydroxyphenyl) -4-methoxycarbonyl-piperidine hydrochloride

+ 1.23 g 2,3-dichloropropene-U)

CH.

2.5 g =

HCl

1- (2-Chlorailyl) -4- (3-hydroxyphenyl) -4-ethoxycarbonyl-piperidine hydrochloride 2.85 g

4- (3-Hydroxyphenyl) -4-hydroxycarbonyl-piperidine hydrochloride

+ 1.23 g 2,3-dichloropropene- (1)

• 5

3.0 g S3, 5%

■ a η η

1-0,3-dichloroallyl) -η- (3-hydroxyphenyl) -A-acetyl-piperldine hydrochloride

2.19 g

^J »- (3-Hydroxypheny 1) ^ -acetyi-piperidine

+ ^ -, 1 E.

1 -Brorri-3,3-dichloropropene- (2)

2/3 g o3 #

207 208

oy

HCl

.Cl

CH ₂ - CK

1- (3,3-Bichlorallyl) -4- (3-hydroxyphenyl) -it-propionyl-piperidine hydrochloride

2.33 g

* »- (3-Hydroxyphenyl; · h -propionyl-piperidine

+ 2, Ig.

1-bromo-3,3-dichloropropene- (2)

2.75 ε

2i8 219

70

1- (3,3-Dichloroallyl) -4- (3-hydroxyphenyl) -4-methoxycarbonyl-peridine hydrochloride rid "2.71 g

.4- (3-Hydroxyphenyl) 4-methoxycarbonylpiperidine hydrochloride

l-broai-3,3-dichloropropene- (2)

809 81 1/106 5

2.7 E.

189 190

14455

18 *; °

Structural structure

cfiem. -fi'ez'eicMuihg

Ausgaiigamateriax

(SULj.

ÄiisfoutW

1- (3.3-Dichlof allyl) -

(3yyjp ίΤ- KtKoxyc arbbhyl - ρ i -pertdin-hythrechloriä 2.85 * g ". \ '"

(^ y ^ TfjT ph ^ i yi) -4-ethoxy.carbonyl-piperidine-hydrochloride

l-bromo-3 »3-dlchloropropene- (2)

1- (2,3-D.lchlprallyl) - k " (3-hydroxypheiorl) - h- acetyl-plperidirihydroehlorld

2.19 g

4- (3-hydroxyphenyl) -4-acetyl-piperidln

. . +. 1.60 g 1,2,3-trichloropropene- (2)

HCl

1- (2,3-DichloriU.lyU -. 4- (3-hydroxyphenyl) -4-propioivl-piperidine hydrochloride

2.33 S.

4- (3-hydroxyphenyl) -4-propionyl-piperidine

+ 1.60 g 1,2,3-1 rlchlorpropene-r

i).

1.7 g -

OH

1- (2,3-Diehlorallyl) • 4- (3-hydroxyphenyl) -4-methoxycarbonyl-piperidine hydrochloride

2.71 S

4- (3-hydroxyphenyl) 4-methoxycarbonylpiperidine-hydrochlo rid

+ 1.60 g

1,2,3-trichloropropene- (2)

1- {2,3-Diehlo «LLlyl) -4 - (^ - hydroxyphenyl) -4-ethoxy carbonyl piperidine hydrochloride 2.85 g

- (3-Hydroxyphenyl) -4-ethoxycarbony1-piperidine hydrochloride

+ 1.60 g

1,2,3-trichloropropene- (2)

els -

1- (3-Bromoallyl) -lf- ( 3-hydroxyphenyl) -4-acttyl-piperidine hydrochloride

2.19 p

4- (3-hydroxyphenyl) • 4-acetyl-piperidine

+ 2.20 g

ice-1,3-dibromopropene- (2)

8 0 9 8 11/10 6

1.8 g 48 *

Xr. ΓΤΤ S tTukt urfornie 1 chemical designation From gangsmat eri q. ^. analogue
Ex. Time
(hours.) yield ... 1.8 g - - 2.6 g - .Fp
° c * öS 2.19 g .48 * 66.5 * 7 1 ^ »^^. OH trans- 4- (3-hydroxyphenyl) - 197> & j) "< Γ Jj ο l- (3-bromoallyl) -4- 4-acetyl-piperidine 77 > * - V, ^ * v3 ^ _rH (3-hydroxyphenyl) -4- 3 2 195 - ^η 78 / S ³ acetyl-piperidine-hy-
hydrochloride + 2.20 g
trana-1,3-dibromopro- 197 ι ^w V _- J • HCl
I. pen- (2) I.
CH ₂ - CK = CHBr 2.4 g = co 2.71 g 212 - cis- 4- (3-hydroxyphenyl) -4- 61.5 21 * I 1 ^ o l _! - (3-bromoallyl) -4- methoxycarbonyl-pipe- ^^^ ^ * '- 0CH_ (3-hydroxyphenyl) -4- ridine hydrochloride 4th 2 methoxycarbony1-pipe- 79 ' L ^ j · HCl ridine hydrochloride. +2.00 g I. eis-i, 3-dibrorapropen-
(2) * 'CH ₂ - CH - CHBr ■ '"- ιΛΙΙ 2.71 g . trana- 4- (3-hydroxyphenyl) - \ A o 4.-Methoxy carbonyl- pi- · '"V ^ * · ^ OCH (3-hydroxyphenyl ) -? - peridine hydrochloride 3 · 2 methoxycarbonyl-pi- - peridine hydrochloride + 2.00 g CH ₂ - CH = CHEr tr? .r.2-i, 3-Librorr.pro- pen-: 2)

1- (2-bromoailyl) -4- (3-hydraxyphenyl) -4-

acetyi-pip'eridin-liy- flrtochlo \ d

. . i. 1'19.Si . . . {τ ^ -Hydroxyphenyl.) 4-aeetyl-piperidine

, 1 * 2-DibroJ5pro5; e »i- (2)

$ 69.5

1- (2-Br «aeH.yl) -4- % 3-hydropcypheny 1) -4-prop! ohyi-piperIdInhyflrochlorld

. . . . 2.23.8. . . . * - (3-Hydro ^ yphenyl) -. 4-propionyl-piperidine

2-dibromoprop ^ nr (2)

-hyd

ih

roj

ineithox yc

yJ. henyl) -4-onyl-'pi'pei-

2.71.8

(jjHydroxypheny ] _t 4j-me tihoxy carboiiy 1 - pi -riejiidiil-nydröcnior ^ d '

; . : t i.qo.g. ι '

, 2-qibroniprppen-; (2)

t -

ΐ i

\ r t-

2.7 8 -70 *

2, 'β Β 68.5

iao.-.

Ί89 190

1445515

Mr, i f I • '^ l- (2-bron; allyl) -4- 2.85 g Belsp. • 2 ,hours.; P Q er ⁰ C ■ Cl 233 (3-hydroxyphenyl) -4- 4 - (^ - hydroxyphenyl) -4- <-> y 6 -
7PgC ,. ^^ <^ 2 ^ üthoxycarbonyl-pipe- ethoxycarbonyl-piperi- I J. HCl ridine hydrochloride din hydrochloride St. I. C. ι R7 ~ » I.
^ ΙΤλ "" ν - vUa + 2.20 g I.
Br 1,2-dibromopropene (2) ^^^ OH 65. H J ^^ 1 - (3,3-Di brcnial IyI) - 4.0 g = V ^ ^C "* -CH 4- (5-hydroxyphenyl) - 2.19 g
4 - (^ - hydroxyphenyl) - Q Qt &
OO / & ^^ 3 4-acetyl-piperldln- 4-acetyl-piperidln Γ *. 1 * HCl hydrochloride b ^; - ι St * + 3.10 κ 2 2 222 CH ₀ - CH = C ^ ₀ 1.3 »3-tribromopro- OH pen- (2) * ι 0 i- (3 # 3 "dibromoallyl) - 2.33 g '. 4.0 g = ^^^ C ^ 4- (3-hydroxyphenyl) - 4- (3-hydroxyphenyl) - 85.5 * 4-propionyl-piperi- 4-propionyl-piperidine din hydrochloride 2 CH ₂ -CH-C
-Br. I. +>, - «- vg
1,3 ', 2-tribromopropene
(2)

'«ΓΠ. I I

86

HCl

- CH

Br

1- (3.3-DibroKallyl) -4- (3-hydroxyphenyl) -4-methoxyeartonylpiperidine hydrochloride

2.71 8

^ - (3-Hydroxyphenyl) -4-methoxycarbonyl-piperidine-hydrochloride

♦ 3.10.8

1.3 »3-tribromopropene

(2)

^ .2 g 89.556

67

* - (5- hydroxyphenyl) -4-ethoxycarbonyl-piperidine hydrochloride 2.85 g

* - (3-Hydroxypheny1) -4-ethoxycarbonyl-piperidine hydrochloride

+ 3.10.8

1 * 3,3-tribromopropene (2)

ClL ₅ -CH-C

3 * 95 β 81.5 Ji

809811/1065

Example 88:

trans-1- (3-chloroallyl) -4- (? -hydroxyphenyl) ~ 4-methoxy- » carbonyl piperidine hydrochloride

a) traHB-1- (3-chloroallyl) -4- (3-ynethoxyphenyl) -4 ~ cyanopiperidine hydrochloride

67to g (0.256 mol) of trans-N- (3-chloroallyl) bis (2-chloroethyl) amine hydrochloride are dissolved in water and removed the solution with concentrated NaOH in the presence of ice, the base is released. After saturating with potassium carbonate is extracted three times with 75 ml of toluene each time “The combined toluene solutions are dried with potassium carbonate and the toluene in vacuo at approx. 40-50 ° C distilled off · The residue is dissolved in 160 ml of absolute ioluene and 37.7 g (0.256 mol) of 3-methoxybenzyl cyanide are added to the solution. In the solution are 30 - 40 ° C with stirring and ice cooling within 20 minutes 21.2 g (0.545 Hol) sodium amide in portions registered. It is then refluxed for 1 hour. After cooling, 100 ml of water are added and the toluene layer is separated off. The toluene solution is shaken with 220 ml of 2N HCl and 1000 ml of water until two clear layers have formed which are separated * The aqueous phase is extracted with toluene and then with ether and then with concentrated Asmoniak made highly alkaline. Who fail

80981 1/1065

COPY

BAD ORIGtNAL

The base is separated off by shaking out three times with 200 ml of ether each time. After drying with Na ₂ SO ^ the ether solution is acidified with ethanolic HCl, the hydrochloride of the base precipitating, which is filtered off with suction and washed with ether. You get 56 g (67 $> of theory) Substans at P = 137 ° C.

b) trans-1- (3-chloroallyl) -4- (3-hydroxyphenyl) -4-carboxypiperidln

25 β (0.074 mol) trans ~ 1 ~ (3-chloroallyl) -4- (3-methoxyphenyl) 4-oyano-piperidine hydrochloride, 42 g of phenol and 190 ml of 48% strength hydrobromic acid are refluxed for 4 hours. It is then cooled, diluted with 190 ml of water and extracted twice with 100 ml of ether each time. The ether extracts are washed with 50 ml of water, the combined acidic aqueous solutions are extracted once with 100 ml of Xtker and evaporated to dryness in vacuo. Are obtained after recrystallization from water 18 g (64 _t 5 i "of theory) of pure hydro bromide from? * 130 ° C and 222 ° 0. A small sample, recrystallized from alcohol / ether, has the 9 - 222 ° C.

Duron LUsen in warmest water (18 g in 225 ml) and neutralize the solution with conc. NH * (pH = 7) is obtained from de »Hydrobromide the free trans-1 ~ (3-chloroallyl) -4- (5-ll3fdroxyphenyl) -4-carboxy-piperidine from P» 273 ° C.

BATH 809811/1065

ο) trans-1- (3-chloroallyl) -4- (3-hydroxypheny1) -4-methoxycarbonyl-piperidine hydrochloride

5.1 g (0.0172 MoX) tra »e-1- (3-chloroallyl) -4- (3-hydroxyphenyl) -4-carboxy-piperidine are added to 50 ml of absolute Ethanol suspended and dl · mixture on the Vaeserbad Bit dry »HCl- (Yes * saturated. This leaves the acid If the oxide is added later, the ester hydrochloride will heat up from «laoh inegesant 3 hours of cooking with introduction ▼ on ROl is cooled and sucked off. The crystals will be Bit methanol / ether washed; the yield is 4.1 g (83.5 Jt of theory) το «F - 217 ° C. Except for a small sample of the hydrochloride, the free one was found Base steeply steeped. She has the F = 141 ° C.

Example 89t

trana-1- (3-chloroallyl) -4 - (^ - hydroxyphenyl) -4-acetyl-piperidip hydrochloride

E (0 * 074 Hol) trans-1 * (3-chloroallyl)> 4 ~ (3-methoxyphenyl)> 4-oyaiio-piperidine hydrochloride are mixed with 100 el water, al 2b latron hydroxide and 75 ■! Beneol was shaken, the benzene sole was separated off and the aqueous solution was shaken again with 7 ml of Beneol. The benzene solutions are terelongated, _{dried with Ia 2} SO ^ and the benzene is evaporated in general vacuum. The residue is gelatinized in absolute benzene, which evaporates again but to dryness, the residue again

BATH 8098 11/1065

η-

dissolved in 50 ml of absolute benzene and this solution is added dropwise to a Grignard solution consisting of methyl magnesium iodide in benzene clay 45 ° C. Sufficient solvent is distilled off from the reaction odor with stirring until the internal temperature has risen to 76 ° C and then stirred at this Temperature 16 hours. The reaction mixture is then poured onto 200 g of ice and 50 g of ammonium chloride and, after heating to 30 ° C., extracted three times with 200 ml of benzene each time. The combined benzene solutions are dried and the solvent evaporated. The residue that remains is ketimine, which is processed further without purification;

Haeh addition of 50 g of phenol and 220 ml of 48 # HBr becomes Boiled under reflux for 4 hours »cooled, diluted with 220 ml of water and extracted twice with 100 ml of ether each time. The ether solutions are washed with 50 ml of water. The combined aqueous solutions are extracted with 100 ml of ether and then evaporated to dryness in vacuo. A residue of 5 g remains when it is dissolved in a little alcohol and acidification with alcoholic HCl as Hydrochloric! crystallized· The yield is 7.4 g (30.5 # of theory) of P »184 ° C (from ethanol / ether).

The trans-N- (3-chloroallyl) -bis- (2-chloroethyl) amine hydrochloride used as the starting substance can be obtained as follows:

⁸⁰⁹⁸¹ V1065 6AD0BIG.NAL

a) trane-I- (3-chloroallyl) -diethanolamine

36.8 g (0.35 Hol) diethanolaain, 42.5 g (0.385 Hol) trane-1 ^ -dichloropropene and 44 g (0.525 mol) jiatrium carbonate earth in 43 al dimethylformamide and 107 ml. Tetrahydrofuran refluxed for 3 hours. The solvent is then evaporated in vacuo and the residue is shaken with 100 ml of water and 75 ml of chloroform. Separating Bach in a separating funnel is shaken out several times with 50 ml of chloroform each time, the combined chloroforal _{solutions are dried with Ha 3} SO ₄ and, after the solvent has been distilled off, the compound is distilled in Yaktnim. After € g forerun, 55.5 g (88 l> of theory) of trane-H- (5 ~ chloroallyl) diethanolamine rom bp _{0 4} = 134-136 ° C. are obtained.

b) tran * -I- (3-chloroallyl) -bis- (2-chloroethyl) amine hydrochloride

46 pounds (0.256 Hol) trans-H- (3-chloroallyl) diethanolamine, dissolved in 50 ml of absolute chloroform, are mixed with 130 g of thionyl chloride (1.1 Hol) in 100 ml of chloroform within 50 minutes with cooling and stirring. AnsohlieBexid is refluxed for 1 hour, cooled and treated with 300 ml of absolute ether. The hydrochloric * des tran »-l- (3-chloroallyl) -bi- (2-chloroethyl) -amine, which crystallizes on standing in the refrigerator, is weighed off and washed with ither. After drying in vacuo, 64 g (100 liters of theory) of the compound mentioned with a melting point of 62 ° 0 (from alcohol / ether) are obtained. BAD ORIGINAL <m-: ■, - '· -' 8098 Ί 1/1065

Claims (2)

Claims Process for the preparation of new haloallylpiperidines the general formula R _{1 is} hydrogen or methyl, R _{2 is} hydrogen, methyl, chlorine or bromine * R-, hydrogen, fluorine, chlorine or bromine _f R. hydrogen, methyl, chlorine or bromine, Rc hydrogen or methyl (a or B) ₉ Rg hydrogen, methyl or chlorine, Methyl, hydroxy, methoxy? Acetoxy, fluorine, chlorine or bromine and Methyl, ethyl, propyl, methoxy, ethoxy or propoxy mean, where each at least one of the best Rg, R * or 809811/1065 - rr - Β. must mean a halogen atom, as well as their acid additionaealeen, characterized in that one a) a secondary piperidine derivative of the formula II, where Se »Hg, R ^ and Hg have the meaning given above have old a compound of the formula Z - CH - C »(T ⁴ III, where Bf «R ₂ , Β«, R * have the meaning given above more often a tosyloxy radical / i »d Z denotes a halogen atom /, alkylated on the nitrogen atom, Torsugeweiee in the presence of an organic solvent and a weak base, or that one b) a J) i- (fl ~ halogenethyl) amine of the formula 809811/1065 CHr R « Rr and E has the meaning given above have, ait a benzyloyanide of the formula where Ü £ and 3L * have the meaning given above, in In the presence of a suitable condensing agent, preferably Vatrlunamid, reacted and ife Hitler ^ il group of the thus obtained cyano compound of the general ornel VI, BATH 80 98 M / Ί where R ₁ , Rg »R ^, H ^ t R ^» Bg and R ^ have the meaning given above, converted into the ester or keto group by saponification and esterification or by Grignardation and hydrolysis of the intermediate ketimine compound, optionally an aa mienyl ring of a compound of Porael I! Hydroxyl group located methylated or acetylated, optionally demefchylated a methoxy group or a Aoetoxy group is saponified, and the end product thus obtained is optionally converted into a physiologically acceptable acid addition salt. 2.. Process according to Claim 1, characterized in that the alkylating agent is used in excess. 3 · The method according to claim 1, characterized in that ■ to an aa phenyl ring of Benaylcyanlda possibly existing Hydroxy group before ring closure by alkylation or Acylation protects. 80981 1/1065 R ₁ hydrogen or methyl » Rg hydrogen, methyl, chlorine or bromine, R- hydrogen, fluorine, chlorine or bromine, R * hydrogen, methyl, chlorine or bromine ₉ Rc hydrogen or methyl (a or ß), Rg hydrogen, methyl or chlorine, R "denotes methyl, hydroxy, methoxy, acetoxy, fluorine, chlorine or bromine, Rg methyl, ethyl, propyl, methoxy, ethoxy or propoxy, but at least one of the radicals R ₂ , R * or R. must be a halogen atom, and whose acid addition salts have valuable pharmaceutical properties. According to the invention, the new compounds can be prepared will: a) By alkylation of a secondary piperidine derivative of formula Jl, 80981 1/1065 wherein Rcν Rg f Β »and Rg have the meaning given above, »It is a compound of the formula S-GH-CC ⁴ -III, R ₁ R ₂ which have the R, R ', R * and R, as defined above and wherein 35 represents a halogen atom or a tosyloxy group . The reaction is preferably carried out in the presence of a suitable organic solvent and a weak base, for example sodium carbonate, expediently at temperatures between 50 and 150 ° C. The reactants can be used in a molar ratio of 1: 1 ; however, the alkylating agent is preferably used in excess . Alcohols or a mixture of dimethylformamide and tetrahydrofuran are used as solvents . 8 0 9811/1 OJ5 Unless otherwise mentioned, a mixture of cis and trans-haloally compounds is used. The end product is then also an eis-trans-Geiaiech, the usual methods, 2. B. by crystallization, into its stereoisomers can be split up. But one can also, as is described variously in the examples, already from a pure ice or go out trans-haloallyl and then get the corresponding cis- or trans-haloallylpiperidine. b) By reacting a pi- (ß = halo-ethyl) ~ amine of the formula ₂ CH ₂
CIU OH ₂ CH - C «C R ₁ R ₂ ^ß 3 80981 1/1065 in which R ₁ , Rg, R *, R ₄ and Z have the meanings given above , alt a Beneyloyanid of the formula - C 5 H in which Rg and R »have the meaning given above and subsequent conversion of the oyano compound of the formula obtained from the formula , R ₇ YI, in which the radicals R ₁ -B _{7 have} the meaning given above , into the Esttr or Ket © compounds of the formula I. The Bingechluß takes place in the presence of a suitable KondensationAlttsle, such as powdered sodium amide, in an inert organic solvent, e.g. B. toluene. she BATH 80981 1/1065 The reaction temperature is generally between 40 and 200 ° C. The oyano compound of the formula VI is obtained in this way The nitrile group is converted into an ester or keto group in the usual way. For example, for the production of end products of the formula I, wherein Bg is an alkoxy group, the nitrile group by Exposure to acids or alkalis saponifies and esterifies. One wishes to obtain as a final product a ketone (R ₈ = alkyl), one uses a compound of formula YI, in the presence of a suitable organic solvent with a corresponding "the Grignard compound to the hydrolyzed and intermediately formed ketimine compound _o If there is to be a hydroxyl group in the end product for the radical R ₅ , it is necessary to protect this before the start of the ring closure reaction by acylation or alkylation. The deaylation of an eo protected hydroxyl group takes place automatically during the saponification of the nitrile or the hydrolysis of the ketimine compound. If there is a hydroxyl group protected by an alkyl radical on the phenyl ring of the cyano compound VI, it is advantageous to carry out the hydrolysis of the nitrile group or the hydrolysis of the ketimine compound using hydrobromic or hydroiodic acid, since the alkyl radical is split off at the same time. BATH ORIGINAL 80981 1/1065 -S - Sine ih an end product obtained according to a) or b) 9OrBeI I any hydroxyl group present can optionally "Ethyli.ert b" w. be acetylated. It is also the other way around «Ogllohts a methoxy group on the phenyl ring deaethylieren be «to saponify an aoetyl group. If desired, a compound of the general formula I into a physiologically harmless acid addition salt are converted into tallow, for example, by treatment with an inorganic or organic acid, such as mineral acids, acetic acid, methanesulfonic acid, tartaric acid, fumaric acid, halic acid, citric acid, ascorbic acid, caproic acid or Propionic acid. Raoh of the invention can e.g. B. the following end products b «w, the acid addition alse of which are obtained: 1- (5-Ohlorallyl) -4-C2-methylphenyl) -4-acetyl-piperldine hydrochloride, piperidine hydrochloride, trane-1- (3-chloroallylM- (2-chlorophenyl) -4-propionyl-piperi- dln hydrochloride, 1 - (3-chloroallyl) -4- (3-chlorophenyl) -4-methoxy-carbonyl- ' piperidine hydrochloride, 1 - (3-chloroallyl) -4- (3-chlorophenyl) -4-ethoxycarbonyl piperidine hydrochloride, 1- (3-chloroallyl) -4- (4-chlorophenyl) -4-propionyl-piperidinhydroohlorld, _8098l 1 - (3-chloroallyl) -4- (4-chlorophenyl) - * 4 ~ methoxyearbonyl piperidine hydrochloride, 1- (3-chlorprallyl) -4- (2,4-dichlorophenyl) -4-propionyl piperidine hydrochloride, 1 - (2-Br © BSEllyl) -4- (4-chlorophenyl) «^ -propionyl-piperidine hydrochloride, 1- (3, 3-J> dichlorallyl) -4- (3-methylphenyl) ~ 4-methoxycarbonyl piperldine hydrochloride, 1- (3-chloroallyl) -4- (3-hydroxyphenyl) -4-acetyl-piperidine hydrcohlorid, 1 - (3-chloroallyl) -4- (3-hydroxyphenyl) -4-yne thoxycarbonyl piperidlnrhydrochloride, 1- (3-chloroallyl) -4- (3-hydroxyphenyl) -4-methoxycarbonyl piperidine hydrochloride, 1 - (3 _f 3-Diöhlorallyl) -4- (3-hydroxyphenyl) -4-ethoxy-carbonyl- » plperidin hydrochloride, 1- (3,3-Dibromoallyl) -4- (3-hydroxyphenyl) -4-m9thoxycarbQnyl piperidine hydrochlorido The new piperidine derivatives are distinguished by an extraordinarily strong morphine-antagonistic effect; some the compounds also have a pronounced similar effect. The new substances can therefore in human medicine as non-humid analgotics or alt additives to addictive anaigetics, for example Morphine, fhetidine or ketobsmidone, find use. 809811/106 They can all be used for pharmaceutical purposes Process preparation molds. For example, you can get out of it I ₉ dragees, tablets »Suppoeitories, emulsions, solutions and create integration solutions. 2.65 C2-methylphenyl-4'-aoetyl-4-> piperidine hydrobromide are dissolved in 10 ml of water, mixed with 10 ml of 2N sodium hydroxide solution and shaken with it. The ethereal solution is dried up, the residue is dissolved in 30 ml of tetrahydrofuran and 15% of methyl alcohol, and 1.3 g of 1,3-dichloropropene (2) and, in particular, 1.5 g of sodium bicarbonate are added. The mixture is heated under reflux for 7 hours, evaporated to dryness in a waterpump vacuum, the residue extracted with chloroform, dried and evaporated for 4 hours of chlorofloride, which is evaporated in methylene chloride, which is ethyl acetate. gelQet and this solution filtered over 60 g of basic aluminum oxide (activity Z). The solvent is then vevdaepft, dtr residue in the above. 5 ml of methanol absorbed by old ethereal hydrobromic acid, weakly acidified, adding ether until weakly cloudy, Aas Hydrobroaid crystallizes out. Ee is recrystallized from methanol / ether. The yield is 2.4 g ( $ 62 of theory). It has the Ρ - 180 - 162 ° G. 809811/1065 Example 2s 1 - (^ -Chl o rallyl) -4- (3 ~ hyd roxyphenyl) * 4 ° aoetyl ° Tf> iperidine- ' hydrochloride 2.18 g (0.010 mol) 4- (3-hydroxyphenyl) ~ 4-acetyl-piperidine, 1.26 g (0/315 mol) NaHCO ₃ and 1.23 g (O ₉ OH mol) 1,3-dichloropropene are refluxed with 10 ml of dimethylformamide and 25 ml of tetrahydrofuran for 2 hours o Then the solvent is removed in vacuo and the residue is rinsed with 50 ml of chloroform in a separator * After shaking out three times with 20 ml of water, the chloroform solution is dried with lagSOj and then the Solvent evaporated in vacuo. The residue is taken up in methanol, acidified with 4 ml of 2.5N alcoholic hydrochloric acid, and ether is added until it becomes cloudy. The abovementioned hydrochloride crystallizes out on heating; leave to stand overnight, vacuum, wash bit of ether and dry. The yield is 1.8 g (54.5 # of theory). The substance has the 2 = 184 ° C (from methanol / ether). Example 3s trans-1 - (3j-chloroallyl) -4- (3-hydroxyphenyl) -4 -m athqxy carbonyl · »piperidine-hydroohlorld 5.44 g (0.02 mol) 4- (3-hydroxyphenyl) -4-methoxycarbonylpiperidine hydrochloride, 4.2 g (0.05 mole) NaMCO ^ and 2.46 g (0.022 mol) of trans-1,3-dichloropropene are refluxed with 10 ml of dimethylformamide and 25 ml of tetrahydrofuran for 2 hours 8098 11/1066 cooked " Then the solvent is removed in vacuo and the residue is rinsed with 50 ml of chloroform in a Soheide triohter , shaking three times with 20 al of water , the Chlorofor" lt5simg dried with Ra ₂ SO ₄ and then the solvent evaporated in vacuo . The residue is taken up in methanol , acidified with 4 ml of 2.5N alcoholic hydrochloric acid, and ether is added until it becomes cloudy. Baoh leaving to stand and filtering off the precipitated crystals srhHt sen 5.9 g (74.5 t of theory) of the hydrochloride from I - 217 - 218 ° C (from methanol / ether), oia-1 - (? - chlorallyl ) -4- (3-hydroxyphenyl) -4 ~ methoxyoarbonyl- 5 * 44 S (0.02 mol) 4- (3-hydroxyphenyl) -4-me1; hoxycarbonyl- fluoridein hydrochloride, 4.2 g (0.05 mol) HaHCO ₃ and 2.46 g (0.022 mol) ois 1,3-Diohlorpropen are boiled under reflux for 2 hours with 10 ml of dimethyl totmamlA and 25-1 tetrahydrofuran. The solvent is then removed in vacuo and the residue is rinsed with 50 ml of chloroform into a Soheide triohter. After shaking out three times with 20 ml each , the chloroform solution is dried with Ha ₂ SO ₄ and the solvent is evaporated in vacuo. The residue Ib methanol was taken up, acidified with 4 ml of 2.5N alcoholic ftaXseaore and ether was added to the point of turbidity. 809811/1065 -Ή - Hau reads standing, filters the crystals that have fallen out and usid receives 6.1 g (77 _f 0 Ji of theory) eie-i- (J-chlorallyl) »· 197 - 198 ° C (st» methanol / ether). Example St - & thoxyoarbonyl piperidines «- Ihof hydrochloride 2t86 £ (0 «01 mol) 4- (3-hydroxyphenyl) -4» ethoxyceurbo7iyl-! »Iperldine hydrochloride, 2.10 g (0.025 Hol) NaHCO ₃ and 1.23 g 1,3-dichloropropene are bit 10 ml Dimethylformamide and 25 ml of tetrehydrofisran boiled under reflux for 2 hours. Subsequently, the LBsungemittel la V _a is kuun removed and the residue ■ it 50 al Chloroforn in a Soheidetrichter rinsed. Kach Drela & ligea Aueechüttel "ait 20 ml Walser, the Ghloroforaiesung old Va ^ SO ^ dried and then dae solvent Ib T ^ kttoa Terdampft · The Hückstand ₉ Bit 4 acidified ml 2.5 N alcoholic hydrochloric acid in methanol up-BOBMn and ait Ither to added to cloudiness. 2.3 g (64 pounds of theory) of the hydrochloride mentioned are obtained at a temperature of 207 ° C. (from ithanol / Xther). Example 6t 1 - (3-Chlorall.vl) ~ 4 ~ (3- »Bethoxyphenyl) -4-ethoxy carbonyl-piperiiim-» aydrochloride 3 74 S (0.01 Hol) 1- (3-chloroallyl) -4- (3-hydroxyphenyl) -4-etho3Qr- 8 0 9811/1065 BAD ORIQJNAU > β Cartonyl piperidine hydrochloride (prepared according to Example 5) are shaken in a separating funnel with 50 ml of chloroform, 25 ml of water and 10 ml of 2N ammonia. The chloroform solution is separated, washed bit 25 ml of water, dried with Na ₂ * BO and then the solvent evaporated. The residue is dissolved in 25 al tetrahydrofuran and 0.0125 mol of diazomethane in ether is added to the solution. After 4 hours the solvent is evaporated, the residue is taken up in chloroform and the chloroform solution is washed twice with 2N sodium hydroxide solution, then with water.After drying with Na ₂ SO ₄ , the chloroform is evaporated, the residue is dissolved in 15 ml of ethanol and the solution Acidified with 4 ml of 2.5N alcoholic hydrochloric acid. After the addition of ether up to cloudiness, 2.5 g (64.5 # of theory) of the above -mentioned hydrochloride with a melting point of 161.5 ° C (from ethanol / ether) crystallize. Example 7 » , ole-1 - (3-chloroallyl) - »4- (^ -» acetoxyphenyl ) ~ 4-methpxy ca rbonyl · » pipridine hydrochloride 4.5 g (0.013 hol) egg 1- (3-chloroallyl) -4- (3-hydroxyphenyl) -4-methoxyoarbonyl-piperidine hydrochloride are dissolved in a chemical of 50 ml absolute pyridine and 5 ml acetic anhydride with stirring ( approx. 10 minutes) and then left to stand for 12 hours at room temperature with the exclusion of inactivity. The solution is then evaporated in vacuo, the bridge is shaken with 75 ml of ether, 50 ml of water, 50 g of ice and 20 ml of 2N sodium hydroxide solution , and the ether layer is separated off and '- ■'"' Ι · ^ * £. ^ Ϊ) Ί χι * w ■' SW 8 0 9 8 11/10 6 5 _BA D OFHG'NAL The aqueous layer is shaken out again with 75 ml of ether. The combined ethereal solutions are washed for 3 milliseconds with Jäiswassar, dried with NanSOj and the solvent is evaporated in vacuo. The residue remains, which is dissolved in 50 ml of absolute ether. When acidifying the solution with 7 il 2 _f 5a
alcoholic hydrochloric acid gives a crystalline precipitate, which is filtered off with suction and washed with absolute ether. This gives 4.9 g (97 $> of theory) of the above hydrochloride of F ■ 173 ° C (from methanol / ether). The following additional examples are listed in a table: _BAD 80981 1/1065