methyl (1R,2R)-2-[(3'-fluoro-4'-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate → (1R,2R)-2-{[4-(3-fluoro-4-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}phenyl)phenyl]carbonyl}cyclopentane-1-carboxylic acid

HRID 9614

반응식

HRID 9614 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([C@@H:31]3[CH2:35][CH2:34][CH2:33][C@H:32]3[C:36]([O:38]C)=[O:37])=[O:30])=[CH:25][CH:24]=2)[CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([O:18][C:19]([F:22])([F:21])[F:20])[CH:15]=[CH:14][C:12]=2[N:13]=1>C1COCC1.O1CCOCC1.[OH-].[Na+]>[F:1][C:2]1[CH:3]=[C:4]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([C@@H:31]3[CH2:35][CH2:34][CH2:33][C@H:32]3[C:36]([OH:38])=[O:37])=[O:30])=[CH:25][CH:24]=2)[CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([O:18][C:19]([F:21])([F:20])[F:22])[CH:15]=[CH:14][C:12]=2[N:13]=1

참가 물질

4

반응물 1

HCID 58681326methyl (1R,2R)-2-[(3'-fluoro-4'-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate

생성물 1

HCID 11444140(1R,2R)-2-{[4-(3-fluoro-4-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}phenyl)phenyl]carbonyl}cyclopentane-1-carboxylic acid수율 80%

시약·촉매·용매 2

HCID 14798Sodium Hydroxide용매HCID 22018518Dioxane tetrahydrofuran용매

실험 절차

In 250-mL round-bottom flask, methyl (1R,2R)-2-[(3′-fluoro-4′-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate (2.53 g, 4.53 mmol) was dissolved in 100 mL of 1:1 THF/dioxane containing 5.0 molar equivalents of 1 N aqueous NaOH. The mixture was stirred at rt overnight. The mixture was concentrated under reduced pressure to a volume of about 20 mL. Ethyl acetate (100 mL), water (30 mL), and 5.1 molar equivalents of 1 N aqueous HCl were added to the mixture. The mixture was transferred to a separation funnel. The organic layer was washed with water (1×50 mL), dried (Na2SO4), and concentrated under reduced pressure. The solid was ultrasonicated in 30 mL acetonitrile and filtered to give the desired compound as a white solid (1.96 g, 80%, 94.5% ee). 1H NMR (400 MHz, DMSO-d6) δ 12.20 (br s, 1 H), 10.60 (bs, 1 H), 8.70 (t, 1 H), 7.60–8.20 (m, 8 H), 7.30 (d, 2 H), 4.70 (q, 1 H), 3.20 (q, 1 H), 2.20 (m, 1 H), 2.00 (m, 1 H), 1.50–1.90 (m, 4 H); LC-MS m/z 545.3 (MH+), ret. time 3.93 min.

후처리

  1. concentrationThe mixture was concentrated under reduced pressure to a volume of about 20 mL
  2. additionEthyl acetate (100 mL), water (30 mL), and 5.1 molar equivalents of 1 N aqueous HCl were added to the mixture
  3. customThe mixture was transferred to a separation funnel
  4. washThe organic layer was washed with water (1×50 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe solid was ultrasonicated in 30 mL acetonitrile
  8. filtrationfiltered

출처 및 근거

ORD 기록
ord-6bc3d9a67d954c3aa8168070a865da7d
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091228B2

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