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Triethylamine → tert-Butyl [(1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]carbamate

HRID 270547
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HRID 270547 반응식
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:4]=1.[C:17]([O:21][C:22]([NH:24][C@@H:25]1[CH2:29][CH2:28][C@:27]([CH:33]([CH3:35])[CH3:34])([C:30](O)=[O:31])[CH2:26]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl.CCOC(C)=O>[CH:33]([C@:27]1([C:30]([N:12]2[CH2:11][CH2:10][N:9]([C:5]3[CH:4]=[C:3]([C:2]([F:15])([F:1])[F:16])[CH:8]=[CH:7][N:6]=3)[CH2:14][CH2:13]2)=[O:31])[CH2:28][CH2:29][C@@H:25]([NH:24][C:22](=[O:23])[O:21][C:17]([CH3:19])([CH3:18])[CH3:20])[CH2:26]1)([CH3:35])[CH3:34]
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참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 112184921-[4-(Trifluoromethyl)pyridin-2-yl]piperazineHCID 60122293(1S,3R)-3-((Tert-butoxycarbonyl)amino)-1-isopropylcyclopentanecarboxylic acid

생성물 1

HCID 59833580tert-Butyl [(1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]carbamate
수율 59.5%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 1-[4-(trifluoromethyl)pyridin-2-yl]piperazine (145 mg, 0.627 mmol), (1S,3R)-3-[(tert-butoxycarbonyl)amino]-1-isopropylcyclopentanecarboxylic acid (140 mg, 0.52 mmol) in methylene chloride (10 mL) was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (253 mg, 0.572 mmol) followed by triethylamine (0.156 mL, 1.12 mmol). After being stirred overnight, the reaction mixture was diluted with EtOAc and washed with saturated NaHCO3. The aqueous layer was extracted with EtOAc three times. The combined organic layers were dried (MgSO4), concentrated and purified by flash chromatography on silica gel (20% EtOAc/hexanes to 40% EtOAc/hexanes) to give 0.15 g of desired product. MS calculated for C24H35F3N4O3: (M+H) 485; found 385.2 (M-Boc+H).

후처리

  1. washwashed with saturated NaHCO3
  2. extractionThe aqueous layer was extracted with EtOAc three times
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by flash chromatography on silica gel (20% EtOAc/hexanes to 40% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-e1e6f7d9d308459b971de3c105b9ab29
출처 데이터셋
uspto-grants-2008_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07449467B2

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