Trifluoroacetic acid → VX-765

HRID 1750932노트

반응식

HRID 1750932 반응식
C([O:5][C:6]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13](=[O:30])[CH:14]([NH:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([Cl:28])[CH:22]=1)[C:15]([CH3:18])([CH3:17])[CH3:16])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:27][C:24]1[CH:25]=[CH:26][C:21]([C:20]([NH:19][CH:14]([C:15]([CH3:16])([CH3:17])[CH3:18])[C:13]([N:9]2[CH2:10][CH2:11][CH2:12][CH:8]2[C:6]([OH:7])=[O:5])=[O:30])=[O:29])=[CH:22][C:23]=1[Cl:28]

참가 물질

5

반응물 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 102034841-[2-(4-Amino-3-chloro-benzoylamino)-3,3-dimethyl-butyryl]-pyrrolidine-2-carboxylic acid tert-butyl ester

생성물 1

HCID 10156704VX-765수율 101%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 4 (15.9 g, 36.3 mmol) in CH2Cl2 (30 mL) was added TFA (trifluoroacetic acetic acid) (30 mL) and the solution stirred at room temperature for 3 hours under N2. The reaction was transferred to a beaker (1 L) and diluted with CH2Cl2 (60 mL). To the solution at 0° C. was added solid NaHCO3 (39 g, 46 mmol) and stirred for 15 minutes'before partitioning between EtOAc (300 mL) and H2O (300 mL). After extraction the aqueous layer was acidified to pH 4-5 and extracted with EtOAc. The organic layer was dried (MgSO4) and evaporated to dryness to give 5 as a white solid (14.0 g, quantitative yield): 1H-NMR (500 MHz, CDCl3) δ1.08 (s, 9H), 1.97-2.22 (m, 3H), 2.29-2.41 (m, 1H), 3.71-3.78 (m, 1H), 3.90-3.98 (m, 1H), 4.55-4.62 (m, 1H), 4.86 (d, 1H), 6.64 (d, 1H), 6.74 (d, 1H), 7.53 (d, 1H), 7.74 (s, 1H). Analytical HPLC (cyano column): 8.24 min. LC-MS (ES+) m/e=382.4 (M+H).

후처리

  1. stirringstirred for 15 minutes'
  2. custombefore partitioning between EtOAc (300 mL) and H2O (300 mL)
  3. extractionAfter extraction the aqueous layer
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer was dried (MgSO4)
  6. customevaporated to dryness

출처 및 근거

ORD 기록
ord-f21b04a38c004d32b2b1c4021f6c50d9
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156880B2

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