Benzyl chloroformate → ((S)-6-tert-butoxycarbonylamino-4,5,6,7-tetrahydro-benzothiazol-2-yl)-carbamic acid benzyl ester

HRID 418349노트

반응식

HRID 418349 반응식
[C:1]([O:5][C:6](=[O:18])[NH:7][C@H:8]1[CH2:17][CH2:16][C:11]2[N:12]=[C:13]([NH2:15])[S:14][C:10]=2[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.Cl[C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30].ClC([O-])=O>C(Cl)Cl>[CH2:32]([O:31][C:29](=[O:30])[NH:15][C:13]1[S:14][C:10]2[CH2:9][C@@H:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:18])[CH2:17][CH2:16][C:11]=2[N:12]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

참가 물질

6

반응물 4

HCID 10387Benzyl chloroformateHCID 81531Diisopropylethylamine2회HCID 21226386CarbonochloridateHCID 49844272tert-butyl N-[(6S)-2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl]carbamate

생성물 1

HCID 59190873((S)-6-tert-butoxycarbonylamino-4,5,6,7-tetrahydro-benzothiazol-2-yl)-carbamic acid benzyl ester수율 91.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
4 °C

실험 절차

Dissolved ((S)-2-Amino-4,5,6,7-tetrahydro-benzothiazol-6-yl)-carbamic acid tert-butyl ester (32.6 g, 121.02 mmol) in 300 mL of CH2Cl2. To this was added DIPEA (41.8 mL, 240 mmol). The mixture was cooled to 4° C. To this was added the benzyl chloroformate (17.8 mL, 125 mmol). The mixture stirred overnight. TLC analysis indicated some starting material remaining. Added 0.3 eq more of chloroformate and 0.3 eq. more of DIPEA. Stirred for 4 h. TLC indicated remaining starting material Quenched with 200 mL of saturated NH4Cl. Washed with 2×200 mL of H2O, 200 mL of Na2CO3 and 1×200 mL of brine. Dried organic phase with MgSO4, filtered and concentrated. Applied to a SiO2 column and purified (5:5 CH2Cl2/hexanes to 9:1 CH2Cl2/MeOH) to give two main fractions. 1H NMR analysis indicated that both fractions were acceptable and they were combined to give 44.5 g of ((S)-6-tert-butoxycarbonylamino-4,5,6,7-tetrahydro-benzothiazol-2-yl)-carbamic acid benzyl ester. 3.06 g of S.M recovered 9%.

후처리

  1. stirringStirred for 4 h
  2. customQuenched with 200 mL of saturated NH4Cl
  3. washWashed with 2×200 mL of H2O, 200 mL of Na2CO3 and 1×200 mL of brine
  4. filtrationDried organic phase with MgSO4, filtered
  5. concentrationconcentrated
  6. customApplied to a SiO2 column and purified (5:5 CH2Cl2/hexanes to 9:1 CH2Cl2/MeOH)
  7. customto give two main fractions

출처 및 근거

ORD 기록
ord-491880b6b5904ea1bf53bc9cc2a907ab
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093266B2

반응 노트

불러오는 중…