Oxalyl chloride → alpha-(R)-(3-(R)-Formyl-4-(S)-(3-fluorophenyl)-pyrrolidin-1-yl)-isopropylacetic acid, para-methoxybenzyl ester

HRID 1068127노트

반응식

HRID 1068127 반응식
[OH:1][CH2:2][C@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)[CH2:6][N:5]([C@H:15]([CH:28]([CH3:30])[CH3:29])[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[O:17])[CH2:4]1.C(Cl)(=O)C(Cl)=O.C(N(C(C)C)CC)(C)C.[Si](OC[C@@H]1[C@@H](C2C=CC=CC=2)CNC1)(C(C)(C)C)(C)C>C(Cl)Cl.C(OCC)(=O)C.CS(C)=O>[CH:2]([C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)[CH2:6][N:5]([C@H:15]([CH:28]([CH3:30])[CH3:29])[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[O:17])[CH2:4]1)=[O:1]

참가 물질

8

반응물 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 21341073(3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-phenylpyrrolidineHCID 131722690alpha-(R)-(3-(S)-(hydroxymethyl)-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)-isopropylacetic acid, para-methoxybenzyl ester

생성물 1

HCID 54425800alpha-(R)-(3-(R)-Formyl-4-(S)-(3-fluorophenyl)-pyrrolidin-1-yl)-isopropylacetic acid, para-methoxybenzyl ester수율 94.5%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

The title compound was prepared from 3.53 g of α-(R)-(3-(S)-(hydroxymethyl)-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)-isopropylacetic acid, para-methoxybenzyl ester (from Step C), 0.89 mL of oxalyl chloride, 1.448 mL DMSO, and 5.924 mL of diisopropylethylamine in 150 mL of CH2Cl2 using a procedure analogous to that described for Aldehyde 1, Step C to provide 3.32 g of the title compound as a yellowish viscous oil (94%) after flash chromatography on silica gel eluting with 15˜35% ethyl acetate in hexanes. RF: 0.38 (20% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3): δ9.64 (d,1.8 Hz, 1H), 7.32˜7.34 (m, 2H), 7.23˜7.28 (m, 1H), 6.87˜6.97 (m, 5H), 5.13 (s, 2H), 3.82 (s, 3H), 3.55 (dd, 7.1 & 14.4 Hz, 1H), 3.25˜3.28 (m, 1H), 3.13˜3.20 (m, 2H), 3.07 (d, 9.6 Hz, 1H), 2.88˜2.93 (m, 1H), 2.66˜2.70 (m, 1H), 2.03˜2.10 (m, 1H), 1.00 (d, 6.4 Hz, 3H), 0.91 (d, 6.6 Hz, 3H).

출처 및 근거

ORD 기록
ord-1813ace2299045e28f9de688cfad8f86
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06248755B1

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