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

HRID 418349ノート

反応式

HRID 418349 の反応式
[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

参加物

6

反応物 4

HCID 10387Benzyl chloroformateHCID 81531Diisopropylethylamine2 回HCID 21226386CarbonochloridateHCID 49844272tert-butyl N-[(6S)-2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl]carbamate

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
4 °C

実験手順

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%.

後処理

  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

出典と根拠

ORDレコード
ord-491880b6b5904ea1bf53bc9cc2a907ab
出典データセット
uspto-grants-2012_01
特許番号
US08093266B2

反応ノート

読み込み中…