Toluene → 3(S)-[(3-chloro-4-cyanophenyl)-(3-chloro-4-fluorophenyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2408870노트

반응식

HRID 2408870 반응식
C1(C)C=CC=CC=1.[C:8]([O:12][C:13]([N:15]1[CH2:19][CH2:18][C@H:17]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([Cl:28])[CH:22]=2)[CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].[Cl:29][C:30]1[CH:37]=[C:36](F)[CH:35]=[CH:34][C:31]=1[C:32]#[N:33].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C(OCC)C.O.O1CCCC1>[C:8]([O:12][C:13]([N:15]1[CH2:19][CH2:18][C@H:17]([N:20]([C:36]2[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[C:30]([Cl:29])[CH:37]=2)[C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([Cl:28])[CH:22]=2)[CH2:16]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

참가 물질

8

반응물 4

HCID 1140TolueneHCID 1090002-Chloro-4-fluorobenzonitrileHCID 2724254Sodium bis(trimethylsilyl)amideHCID 666570713(S)-(3-chloro-4-fluorophenylamino)pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 666572273(S)-[(3-chloro-4-cyanophenyl)-(3-chloro-4-fluorophenyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester수율 77.7%

시약·촉매·용매 3

HCID 962Water용매HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

실험 절차

To an anhydrous toluene solution containing 3(S)-[(3-chloro-4-fluorophenyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester (0.50 g, 1.6 mmol) and 2-chloro-4-fluorobenzonitrile (0.30 g, 1.9 mmol) was added a 1.45 ml tetrahydrofuran solution containing sodium bis(trimethylsilyl)amide (1.1 M) using a syringe. The mixture was heated under reflux under a nitrogen atmosphere for 8 hours and cooled to room temperature. Water was added to the reaction solution, and extraction with diethyl ether was conducted. After drying over sodium sulfate and concentration under reduced pressure, the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1). The purified product was concentrated to dryness under reduced pressure to thereby obtain 0.56 g of white amorphous solid 3(S)-[(3-chloro-4-cyanophenyl)-(3-chloro-4-fluorophenyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester.

후처리

  1. temperatureThe mixture was heated
  2. temperatureunder reflux under a nitrogen atmosphere for 8 hours
  3. dry with materialAfter drying over sodium sulfate and concentration under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1)
  5. concentrationThe purified product was concentrated to dryness under reduced pressure

출처 및 근거

ORD 기록
ord-f2b96b6e2aa3495cbbf12a45163a33e4
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815871B2

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