Thiazole → (R)-tert-Butyl 2,2,4-trimethyl-4-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl)thiazol-2-yl)oxazolidine-3-carboxylate

HRID 2357081노트

반응식

HRID 2357081 반응식
[CH3:1][C:2]1([CH3:40])[N:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@@:5]([CH3:39])([C:14](=O)[NH:15][CH2:16][C:17]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])=[C:21]([C:34]([F:37])([F:36])[F:35])[CH:20]=2)=O)[CH2:4][O:3]1.[S:41]1C=CN=C1>>[CH3:1][C:2]1([CH3:40])[N:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@@:5]([CH3:39])([C:14]2[S:41][C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])=[C:21]([C:34]([F:37])([F:36])[F:35])[CH:20]=3)=[CH:16][N:15]=2)[CH2:4][O:3]1

참가 물질

3

반응물 2

HCID 9256ThiazoleHCID 59384447(R)-tert-Butyl 2,2,4-trimethyl-4-(2-(4-(octyloxy)-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)oxazolidine-3-carboxylate

생성물 1

HCID 59384295(R)-tert-Butyl 2,2,4-trimethyl-4-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl)thiazol-2-yl)oxazolidine-3-carboxylate

실험 절차

The synthesis of 2,5-substituted thiazoles is described in Scheme 9. Reaction of the desired alcohol para-methoxybenzyl alcohol (PMB-OH) with substituted 4-fluoroacetophenone 1 afforded the acetophenone intermediate 2. Acetophenone intermediate 2 was then converted to the corresponding bromo-acetophenone using Bu4NBr3 which, upon reaction with NaN3, provided the azido-acetophenone intermediate. Hydrogenation of the azido-acetophenone intermediate afforded amine 3, followed by coupling with orthogonally protected amino acid 4 gave amide 5. Removal of PMB group under hydrogenation gave phenol 6. Mitsunobu reaction of the phenol 6 with the desired alcohol followed by thiazole formation under Lawesson's reagent conditions afforded intermediate 7 in good yield. Removal of the protecting group from intermediate 7 afforded the final amino-alcohol 8.

후처리

  1. customRemoval of PMB group under hydrogenation
  2. customgave phenol 6

출처 및 근거

ORD 기록
ord-8492565283ce4a8bb3b99189b34c3e76
출처 데이터셋
uspto-grants-2010_07
특허 번호
US07759370B2

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