DK174822B1 - Antihypercholesterolæmiske tetrazolforbindelser, mellemprodukter og fremgangsmåde til fremstilling deraf - Google Patents

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Publication number

DK174822B1

DK174822B1 DK198800972A DK97288A DK174822B1 DK 174822 B1 DK174822 B1 DK 174822B1 DK 198800972 A DK198800972 A DK 198800972A DK 97288 A DK97288 A DK 97288A DK 174822 B1 DK174822 B1 DK 174822B1

Authority

DK

Denmark

Prior art keywords

methyl

tetrazol

bis

fluorophenyl

formula

Prior art date

1987-02-25

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• -1 tetrazole compounds Chemical class 0.000 title claims description 195
• 238000000034 method Methods 0.000 title claims description 68
• 238000002360 preparation method Methods 0.000 title claims description 32
• 230000008569 process Effects 0.000 title claims description 9
• 239000000543 intermediate Substances 0.000 title description 17
• 230000000326 anti-hypercholesterolaemic effect Effects 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims description 412
• 229910052739 hydrogen Inorganic materials 0.000 claims description 270
• 238000006243 chemical reaction Methods 0.000 claims description 258
• 229910052757 nitrogen Inorganic materials 0.000 claims description 202
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 186
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 125
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 71
• 125000000217 alkyl group Chemical group 0.000 claims description 58
• 239000001257 hydrogen Substances 0.000 claims description 53
• 239000011734 sodium Substances 0.000 claims description 53
• 150000002431 hydrogen Chemical group 0.000 claims description 43
• 229910052708 sodium Inorganic materials 0.000 claims description 42
• 239000002253 acid Substances 0.000 claims description 39
• 150000003839 salts Chemical class 0.000 claims description 39
• 239000003960 organic solvent Substances 0.000 claims description 37
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 36
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
• 231100000252 nontoxic Toxicity 0.000 claims description 24
• 230000003000 nontoxic effect Effects 0.000 claims description 24
• 150000002596 lactones Chemical class 0.000 claims description 21
• 125000003545 alkoxy group Chemical group 0.000 claims description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 19
• 150000002367 halogens Chemical group 0.000 claims description 19
• 239000012279 sodium borohydride Substances 0.000 claims description 19
• 229910000033 sodium borohydride Inorganic materials 0.000 claims description 19
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
• 150000002148 esters Chemical group 0.000 claims description 13
• 229910052700 potassium Inorganic materials 0.000 claims description 13
• 230000007062 hydrolysis Effects 0.000 claims description 12
• 238000006460 hydrolysis reaction Methods 0.000 claims description 12
• 239000000460 chlorine Chemical group 0.000 claims description 10
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
• HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 claims description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 9
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
• IBZBXKKSBMPSJO-UHFFFAOYSA-N 3,3-bis(4-fluorophenyl)-2-(1-methyltetrazol-5-yl)prop-2-enal Chemical group CN1N=NN=C1C(C=O)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 IBZBXKKSBMPSJO-UHFFFAOYSA-N 0.000 claims description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 239000011737 fluorine Chemical group 0.000 claims description 7
• 229910052731 fluorine Inorganic materials 0.000 claims description 7
• OMAFFHIGWTVZOH-UHFFFAOYSA-N 1-methyltetrazole Chemical compound CN1C=NN=N1 OMAFFHIGWTVZOH-UHFFFAOYSA-N 0.000 claims description 6
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
• 229910052801 chlorine Inorganic materials 0.000 claims description 6
• 150000003536 tetrazoles Chemical class 0.000 claims description 6
• 229930194542 Keto Natural products 0.000 claims description 5
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 5
• 125000001153 fluoro group Chemical group F* 0.000 claims description 5
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 5
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
• 229910000085 borane Inorganic materials 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• 150000004682 monohydrates Chemical class 0.000 claims description 4
• SHJCSBYIGNIKHH-UHFFFAOYSA-N (4-fluorophenyl) 3,5-dihydroxy-8-(1-methyltetrazol-5-yl)nona-6,8-dienoate Chemical compound CN1N=NN=C1C(=C)C=CC(O)CC(O)CC(=O)OC1=CC=C(F)C=C1 SHJCSBYIGNIKHH-UHFFFAOYSA-N 0.000 claims description 3
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
• PTLLZUCFXRCXMZ-UHFFFAOYSA-N 5,5-bis(2-fluoro-4-methylphenyl)-4-(1-methyltetrazol-5-yl)penta-2,4-dienal Chemical compound FC1=CC(C)=CC=C1C(C=1C(=CC(C)=CC=1)F)=C(C=CC=O)C1=NN=NN1C PTLLZUCFXRCXMZ-UHFFFAOYSA-N 0.000 claims description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
• 150000001718 carbodiimides Chemical class 0.000 claims description 3
• 239000011591 potassium Substances 0.000 claims description 3
• DLNIERDUTYVQMH-UHFFFAOYSA-N 2-(1-methyltetrazol-5-yl)-3,3-diphenylprop-2-enal Chemical compound CN1N=NN=C1C(C=O)=C(C=1C=CC=CC=1)C1=CC=CC=C1 DLNIERDUTYVQMH-UHFFFAOYSA-N 0.000 claims description 2
• CSIQUBMEJWWECT-UHFFFAOYSA-N 2-(4-fluorophenyl)-3,5-dihydroxy-8-(2-methyltetrazol-5-yl)nona-6,8-dienoic acid Chemical compound FC1=CC=C(C=C1)C(C(=O)O)C(CC(C=CC(=C)C=1N=NN(N1)C)O)O CSIQUBMEJWWECT-UHFFFAOYSA-N 0.000 claims description 2
• QZZAPDSIUDNXOH-UHFFFAOYSA-N 3,3-bis(2-fluoro-4-methylphenyl)-2-(1-methyltetrazol-5-yl)prop-2-enal Chemical compound FC1=CC(C)=CC=C1C(C=1C(=CC(C)=CC=1)F)=C(C=O)C1=NN=NN1C QZZAPDSIUDNXOH-UHFFFAOYSA-N 0.000 claims description 2
• GLPLJOUOYCRBQE-UHFFFAOYSA-N 3,3-bis(4-methoxyphenyl)-2-(1-methyltetrazol-5-yl)prop-2-enal Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)=C(C=O)C1=NN=NN1C GLPLJOUOYCRBQE-UHFFFAOYSA-N 0.000 claims description 2
• UKOOAWXXSCBIAV-UHFFFAOYSA-N 3-(2,4-dimethylphenyl)-2-(1-methyltetrazol-5-yl)prop-2-enal Chemical compound CC1=C(C=CC(=C1)C)C=C(C=O)C1=NN=NN1C UKOOAWXXSCBIAV-UHFFFAOYSA-N 0.000 claims description 2
• WMHRYMDGHQIARA-UHFFFAOYSA-N 4-hydroxyoxan-2-one Chemical compound OC1CCOC(=O)C1 WMHRYMDGHQIARA-UHFFFAOYSA-N 0.000 claims description 2
• PKCKEZQWMULFSP-UHFFFAOYSA-N 9,9-bis(4-fluorophenyl)-3-hydroxy-8-(1-methyltetrazol-5-yl)-5-oxonona-6,8-dienoic acid Chemical compound CN1N=NN=C1C(C=CC(=O)CC(O)CC(O)=O)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 PKCKEZQWMULFSP-UHFFFAOYSA-N 0.000 claims description 2
• WBNCQMSGKFHQRN-UHFFFAOYSA-N FC1=CC(=C(C=C1)C=C(C=O)C1=NN=NN1C)C Chemical compound FC1=CC(=C(C=C1)C=C(C=O)C1=NN=NN1C)C WBNCQMSGKFHQRN-UHFFFAOYSA-N 0.000 claims description 2
• 230000003213 activating effect Effects 0.000 claims description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
• NKXBWPXYRBYYRR-UHFFFAOYSA-N ethyl 9,9-bis(4-fluorophenyl)-5-hydroxy-8-(1-methyltetrazol-5-yl)-3-oxonona-6,8-dienoate Chemical group N=1N=NN(C)C=1C(C=CC(O)CC(=O)CC(=O)OCC)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 NKXBWPXYRBYYRR-UHFFFAOYSA-N 0.000 claims description 2
• NHVBCCFKFPNKJK-UHFFFAOYSA-N (4-fluorophenyl) 5-hydroxy-8-(1-methyltetrazol-5-yl)-3-oxonona-6,8-dienoate Chemical compound CN1N=NN=C1C(=C)C=CC(O)CC(=O)CC(=O)OC1=CC=C(F)C=C1 NHVBCCFKFPNKJK-UHFFFAOYSA-N 0.000 claims 2
• RCWZCAUZIMZGQB-UHFFFAOYSA-N (4-fluoro-2-methylphenyl) 5-hydroxy-8-(1-methyltetrazol-5-yl)-3-oxonona-6,8-dienoate Chemical compound FC1=CC(=C(C=C1)OC(CC(CC(C=CC(=C)C1=NN=NN1C)O)=O)=O)C RCWZCAUZIMZGQB-UHFFFAOYSA-N 0.000 claims 1
• LKVYRSHPKSBTOH-UHFFFAOYSA-N (4-fluorophenyl) 3,5-dihydroxy-8-(1-propan-2-yltetrazol-5-yl)nona-6,8-dienoate Chemical compound CC(C)N1N=NN=C1C(=C)C=CC(O)CC(O)CC(=O)OC1=CC=C(F)C=C1 LKVYRSHPKSBTOH-UHFFFAOYSA-N 0.000 claims 1
• MBBMXKCOQGGNBU-OALUTQOASA-N (4S,6R)-6-[4,4-bis(4-fluoro-2-methylphenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical group FC1=CC(=C(C=C1)C(=C(C=C[C@H]1C[C@@H](CC(O1)=O)O)C1=NN=NN1C)C1=C(C=C(C=C1)F)C)C MBBMXKCOQGGNBU-OALUTQOASA-N 0.000 claims 1
• MJJWVTSDHVPFSY-OALUTQOASA-N (4S,6R)-6-[4,4-bis(4-fluorophenyl)-3-(2-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NC(C(C=C[C@@H]2OC(=O)C[C@@H](O)C2)=C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=N1 MJJWVTSDHVPFSY-OALUTQOASA-N 0.000 claims 1
• MPEVDFCPPRYIHD-UHFFFAOYSA-N 2-(2,4-dimethylphenyl)-3,5-dihydroxy-8-(1-methyltetrazol-5-yl)nona-6,8-dienoic acid Chemical compound CC1=C(C=CC(=C1)C)C(C(=O)O)C(CC(C=CC(=C)C1=NN=NN1C)O)O MPEVDFCPPRYIHD-UHFFFAOYSA-N 0.000 claims 1
• NPNUEPHXWBLWBS-UHFFFAOYSA-N 3,5-dihydroxy-2-(4-methoxyphenyl)-8-(1-methyltetrazol-5-yl)nona-6,8-dienoic acid Chemical compound COC1=CC=C(C=C1)C(C(=O)O)C(CC(C=CC(=C)C1=NN=NN1C)O)O NPNUEPHXWBLWBS-UHFFFAOYSA-N 0.000 claims 1
• HCNRPZKESLPGRU-UHFFFAOYSA-N 3-(4-fluorophenyl)-2-(1-methyltetrazol-5-yl)-3-phenylprop-2-enal Chemical compound CN1N=NN=C1C(C=O)=C(C=1C=CC(F)=CC=1)C1=CC=CC=C1 HCNRPZKESLPGRU-UHFFFAOYSA-N 0.000 claims 1
• OCJQMPKIWYDAOA-UHFFFAOYSA-N 4-(1-methyltetrazol-5-yl)-5,5-diphenylpenta-2,4-dienal Chemical compound CN1N=NN=C1C(C=CC=O)=C(C=1C=CC=CC=1)C1=CC=CC=C1 OCJQMPKIWYDAOA-UHFFFAOYSA-N 0.000 claims 1
• RMRQAELGUNAGCN-UHFFFAOYSA-N 5,5-bis(4-fluorophenyl)-4-(2-trityltetrazol-5-yl)penta-2,4-dienal Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)=C(C=CC=O)C1=NN(C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)N=N1 RMRQAELGUNAGCN-UHFFFAOYSA-N 0.000 claims 1
• VDGAIWBTPXWGRK-UHFFFAOYSA-N 5-(4-fluorophenyl)-4-(1-methyltetrazol-5-yl)-5-phenylpenta-2,4-dienal Chemical compound CN1N=NN=C1C(C=CC=O)=C(C=1C=CC(F)=CC=1)C1=CC=CC=C1 VDGAIWBTPXWGRK-UHFFFAOYSA-N 0.000 claims 1
• HPFIYXJJZZWEPC-UHFFFAOYSA-N 9,9-bis(4-fluorophenyl)-3,5-dihydroxy-8-(1-methyltetrazol-5-yl)nona-6,8-dienoic acid Chemical compound CN1N=NN=C1C(C=CC(O)CC(O)CC(O)=O)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 HPFIYXJJZZWEPC-UHFFFAOYSA-N 0.000 claims 1
• 241000234282 Allium Species 0.000 claims 1
• 235000002732 Allium cepa var. cepa Nutrition 0.000 claims 1
• JFAFTWVUWYFSHT-OALUTQOASA-N FC1=CC=C(C=C1)C(=C(C=C[C@H]1C[C@@H](CC(O1)=O)O)C1=NN=NN1C)C1=CC=CC=C1 Chemical group FC1=CC=C(C=C1)C(=C(C=C[C@H]1C[C@@H](CC(O1)=O)O)C1=NN=NN1C)C1=CC=CC=C1 JFAFTWVUWYFSHT-OALUTQOASA-N 0.000 claims 1
• 239000004305 biphenyl Substances 0.000 claims 1
• OMVAHPHDNKBAFH-UHFFFAOYSA-N ethyl 5-hydroxy-9,9-bis(4-methoxyphenyl)-8-(1-methyltetrazol-5-yl)-3-oxonona-6,8-dienoate Chemical compound N=1N=NN(C)C=1C(C=CC(O)CC(=O)CC(=O)OCC)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 OMVAHPHDNKBAFH-UHFFFAOYSA-N 0.000 claims 1
• RFHCQXKMLJRJPH-UHFFFAOYSA-N ethyl 9,9-bis(2,4-dimethylphenyl)-5-hydroxy-8-(1-methyltetrazol-5-yl)-3-oxonona-6,8-dienoate Chemical compound N=1N=NN(C)C=1C(C=CC(O)CC(=O)CC(=O)OCC)=C(C=1C(=CC(C)=CC=1)C)C1=CC=C(C)C=C1C RFHCQXKMLJRJPH-UHFFFAOYSA-N 0.000 claims 1
• GZAWXFJYOOXFQC-UHFFFAOYSA-N ethyl 9-(4-fluorophenyl)-5-hydroxy-8-(1-methyltetrazol-5-yl)-3-oxo-9-phenylnona-6,8-dienoate Chemical compound N=1N=NN(C)C=1C(C=CC(O)CC(=O)CC(=O)OCC)=C(C=1C=CC(F)=CC=1)C1=CC=CC=C1 GZAWXFJYOOXFQC-UHFFFAOYSA-N 0.000 claims 1
• KVCLUZWIPQFFEZ-UHFFFAOYSA-N methyl 5-hydroxy-8-(1-methyltetrazol-5-yl)-3-oxo-9,9-diphenylnona-6,8-dienoate Chemical compound N=1N=NN(C)C=1C(C=CC(O)CC(=O)CC(=O)OC)=C(C=1C=CC=CC=1)C1=CC=CC=C1 KVCLUZWIPQFFEZ-UHFFFAOYSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 386
• 239000000243 solution Substances 0.000 description 351
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 339
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 253
• 238000005481 NMR spectroscopy Methods 0.000 description 225
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 186
• 239000000203 mixture Substances 0.000 description 175
• 235000019439 ethyl acetate Nutrition 0.000 description 146
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 111
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 99
• 238000004458 analytical method Methods 0.000 description 98
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 96
• 239000000047 product Substances 0.000 description 81
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 78
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 69
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 69
• 238000002329 infrared spectrum Methods 0.000 description 68
• 230000002829 reductive effect Effects 0.000 description 66
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
• 239000011541 reaction mixture Substances 0.000 description 61
• 239000012044 organic layer Substances 0.000 description 57
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 55
• 239000000741 silica gel Substances 0.000 description 51
• 229910002027 silica gel Inorganic materials 0.000 description 51
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 50
• 239000002904 solvent Substances 0.000 description 48
• 150000001299 aldehydes Chemical class 0.000 description 46
• 238000003756 stirring Methods 0.000 description 46
• 239000007787 solid Substances 0.000 description 44
• 238000004809 thin layer chromatography Methods 0.000 description 43
• 238000010992 reflux Methods 0.000 description 41
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 38
• 239000003921 oil Substances 0.000 description 38
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
• 238000010828 elution Methods 0.000 description 31
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 29
• 239000000725 suspension Substances 0.000 description 29
• 239000003480 eluent Substances 0.000 description 26
• 238000001704 evaporation Methods 0.000 description 26
• 229910052786 argon Inorganic materials 0.000 description 25
• 230000008020 evaporation Effects 0.000 description 25
• 239000007858 starting material Substances 0.000 description 23
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 22
• 239000000284 extract Substances 0.000 description 22
• 238000010898 silica gel chromatography Methods 0.000 description 22
• LALRXNPLTWZJIJ-UHFFFAOYSA-N triethylborane Chemical compound CCB(CC)CC LALRXNPLTWZJIJ-UHFFFAOYSA-N 0.000 description 22
• 230000015572 biosynthetic process Effects 0.000 description 21
• 238000004587 chromatography analysis Methods 0.000 description 21
• 238000004440 column chromatography Methods 0.000 description 21
• 238000001816 cooling Methods 0.000 description 21
• 230000009467 reduction Effects 0.000 description 20
• 238000000746 purification Methods 0.000 description 19
• 235000012000 cholesterol Nutrition 0.000 description 18
• LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 18
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 18
• 229910000104 sodium hydride Inorganic materials 0.000 description 17
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
• 239000002585 base Substances 0.000 description 16
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
• 239000003153 chemical reaction reagent Substances 0.000 description 15
• 239000010410 layer Substances 0.000 description 15
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