JPS595147A - Preparation of 2-amino-1-phenyl-1-propanol derivative - Google Patents

Abstract

PURPOSE:To prepare the titled compound in a relatively high yield, by the ring- opening reaction of a phenylpropylene oxide derivative with an amine derivative or an amide derivative under specific condition. CONSTITUTION:The objective compound of formula III can be prepared by reacting the phenylpropylene oxide derivative of formula I (X is H, halogen, etc.) with the amine devivative or amide derivative of formula II (Y is H, MgBr, etc.; R1 and R2 are H, 1-6C alkyl, etc., or together form a 4-6C N-containing ring) in a proper solvent (e.g. dioxane) under mixing and heating, under atmospheric or possitive pressure. EFFECT: The objective compound can be obtained in one step.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 2-amino-1-phenyl-1-propatol derivatives.

To describe the manufacturing method in more detail, according to the present invention, the general formula (I) (wherein X is a hydrogen atom, a hydrogen atom, a hydroxyl group,
A phenylpropylene oxide derivative represented by the general formula (11) (representing a hydroxyl group with a shielding group such as a benzyloxy group, a methoxy group, or an aceloxy group), and a phenylpropylene oxide derivative represented by the general formula (11) (wherein Y is a hydrogen atom or MgBr, Mρ, M
, I, and R2 and R2 are the same or different and are hydrogen atoms.

An amine derivative or amide derivative represented by an alkyl group having 1 to 6 carbon atoms, an aralkyl group, or a nitrogen-containing ring bonded with 4 to 6 carbon atoms is mixed and heated in an appropriate solvent, or The reaction is carried out under pressure. However, in the formula, X represents a hydroxyl group with a protecting group such as a hydrogen atom, a halogen atom, a hydroxyl group, a benzyloxy group, a methoxy group, an acetoxy group,
Eight and bird are the same or different, hydrogen atom, carbon number 1-
6 alkyl group, aralkyl group, or 2-
Amino-1-phenyl-1-propatol derivatives can be obtained in relatively good yield. Here, examples of alkyl groups include methyl, ethyl, propyl, isopropyl, and butyl.

Secondary butyl, amyl, inamyl, hexyl groups, etc.
Aralkyl groups include benzyl, phenethyl groups, etc.
Examples of the nitrogen-containing ring include pyrrolidine, substituted pyrrolidine, piperidine, and substituted piperidine.

The general method for synthesizing K, 2-7mi/-1-phenyl-1-propatur derivatives is carried out by subjecting the corresponding α-aminoprobiofetun derivative to catalytic reduction or sodium borohydride reduction. However, according to the present invention, -
Specifically, 2-amino-1-7enyl 1. -Propertool derivatives can be produced.

The present invention will be explained below with reference to Examples, but is not limited thereto.

Example-1 1-Phenyl-1,2-furopylene oxide.

2.62 and piperidine, 2.6y with dioxane +
Dissolve at 10 mN and heat under reflux for 15 hours. Then, after driving off the dioxane, the residue was recrystallized from hexane-ether to give 2-piperazino-1-phenyl-1-propatol 2 as colorless needles with a melting point of 84-85°C.
．． I got 5y (57,6 meters).

Br 1, R, νl1laX cm-1 3250 (OH) NMRODO/, δ: ppm (TMS) 0.8
0 (3H two lanes J=7.0Hz CHO■ζ)
125 to 1.90 (6H multiplet piperidine ring) (・Th□ 2.20 to 2.80 (5H multiplet MlfM -0dan-MuC&-) 3.90 (1)] Broad singlet) 4.
70 (IH double line J=4.0H2-an(on)
-) 7.21 (5H-double aromatic ring proton) Example-2 1-(4-methoxyphenyl) -1,2-propylene oxide 6.2 and N,N-diethylamine 1.5
2 was dissolved in toluene 15- and then heated under reflux for 15 hours. After expelling the toluene, the residue was recrystallized from hexane-ether and crystallized into colorless prisms to give 1
-(4-Methoxyphenyl)-2-N,N-diethylamino-1-propatol 3.0y (63.5%) was obtained.

Br ■”” vmax C1' 3220 (OH) NMRC! DC/, δ: PPm (TMS) 0.86
(5H doublet, T-=7.OH,,CH-0Δ)0.
97 (6HEX ray J = 7. OR2N (O
H, CH, ) )2.46 (4H4NHJ-zone
2 N (('convex cH,)) 2.95 (IH pair of quartets J, = 7.0Hz, J, = 4.8H2-CH-C
) 3.70 (3H-double line -ocnS) 4.10
(IH wide single line Odan) 4.63 (IH double line J=4.8H2-0H(OH)-)6.50~7.4
0 (4H quartet aromatic ring proton) Example-6゜1-(4-benzyloxyphenyl) - 2.2y of 1,2-propylene oxide and 1.9y of 4-benzylpiperidine were dissolved in 15+ne of toluene and heated. Reflux 20
Do time. Then, toluene was expelled and the residue was P+ bound with ethanol to form 1-(4-benzyloxyphenyl).
-2-(4-benzylpiperidino)-1-gropanol 2.3y (59%) was obtained as colorless scale crystals.

Br "" vmaX cs ' 15O NMRCD (J, δ: ppm (TME+) 0.
81 (3H double line J=7.0H2-OH-C!H,
) U? U practice 5.90 (IH wide single line) 4.74 (IH double line J”'5.OHz C
H(OH) )5.00 (2H-heavy line pj-a
n, -o) 6.70-7.60 (14H multiplet aromatic ring proton) elemental analysis C□H□No.

Calculated value a, 80.92 H, 8, LION,
3.37 Experimental value c, 81.0On, 7.92
N, 3.50 Example-4゜Magnesium 1.2F+ Iodine 10m THF30+
++t! After stirring and keeping at 20°C, 6.51 f of ethyl bromide was added dropwise to make ethylmagnesium bromide, and at the same temperature, 20 ml of THF solution containing 4-benzylpiperidine 91y was added. It was added dropwise, then stirred at the same temperature for 1 hour, further cooled to 10°C, and 10 e of a THFHF solution containing 3.0y of 1-(4-hydroxyphenyl)-1,2-7"ropylene oxide was added. After stirring at the same temperature for 2 hours, the mixture was poured into a saturated ammonium chloride water bath for decomposition, extracted with ethyl acetate, washed with water, dried (@magnesium acid), and concentrated to obtain a residue of 10.0 y. After separating and purifying the residue using silica gel column chromatography, the distillate was recrystallized using isopropanol to obtain a melting point of 110-1.
2-(4-Benzylpiperidino)-1-(4-hydroxyphenyl)-1-gropanol 4.2y (65.1%) was obtained as colorless crystals at 15°C.

3250 (OH) NMRCD(E/, -DMSO-(16ppm(TMS
)0.81 (3H double line J=7.OH,,0H-
0 ships) 4.50 (IH double line J = 5.5H2-
cn(oH)-)5.50 (2H broad singlet p
-OH0H-OH) 6.47~7.22 (9H multi-lane
aromatic ring proton) or more

Claims (1)

[Claims] General formula (I) (wherein, X is a hydrogen atom), a rogene atom, a hydroxyl group,
A phenylpropylene oxide derivative represented by a benzyloxy group, a methoxy group, an acetoxy group, or a hydroxyl group attached to a protecting group is represented by the general formula (IT) (wherein Y is a hydrogen atom or MyBr+ Myα+
4I represents R1 and R1 are the same or different and are a hydrogen atom, an alkyl group having 1 to 2 carbon atoms, or an aralkyl group. Or, the general formula is characterized in that the ring is opened at normal pressure or under pressure with an amine derivative or amide derivative represented by the following: m> I R2 (However, in the formula, X is a hydrogen atom or a halogen atom, and waterfowl is the same as -
Or, differently, a hydrogen atom, an alkyl group having 1 to 6 carbon atoms,
A method for producing a 2-amino-1-phenyl-1-propanol derivative represented by an aralkyl group or a nitrogen-containing ring having 4 to 6 carbon atoms.