Water → 1,3-Thiazol-5-ylmethyl N-((1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentyl)carbamate

HRID 52740

反応式

HRID 52740 の反応式
Cl.Cl.[NH2:3][C@H:4]([C@@H:12]([OH:23])[CH2:13][C@@H:14]([NH2:22])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C1(B(O)O)C=CC=CC=1.O.[N+](C1C=CC([O:43][C:44]([O:46][CH2:47][C:48]2[S:52][CH:51]=[N:50][CH:49]=2)=O)=CC=1)([O-])=O>C1(C)C=CC=CC=1.CN(C=O)C.Cl>[NH2:22][C@@H:14]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:13][C@H:12]([OH:23])[C@@H:4]([NH:3][C:44]([O:46][CH2:47][C:48]1[S:52][CH:51]=[N:50][CH:49]=1)=[O:43])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

参加物

8

反応物 4

HCID 962WaterHCID 66827Phenylboronic AcidHCID 98821474-Nitrophenyl 1,3-thiazol-5-ylmethyl carbonateHCID 22864111HCID 22864111、化合物

生成物 1

HCID 111019781,3-Thiazol-5-ylmethyl N-((1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentyl)carbamate

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid溶媒HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
-60 °C

実験手順

The product of Example 66F (9.5 g, 33.4 mmol) and phenylboronic acid (4.1 g, 33.6 mmol) were combined in toluene (150 mL) and refluxed for 2.5 hours with azeotropic water removal (Dean-Stark trap). Toluene (100 mL) was distilled out at atmospheric pressure, then the remaining toluene was removed under vacuum, to provide a yellow syrup which was dissolved in DMF (50 mL) and cooled to -60° C. A solution of 5-(p-nitrophenyloxycarbonyloxy-methyl)thiazole (9.5 g, 33.5 mmol)in DMF (50 mL) was added over 45 minutes. The resulting mixture was stirred for 8 hours at -55°±5° C., then 14 hours at -25° C., then was allowed to warm to room temperature. The reaction mixture was diluted with 1N HCl (250 mL) and washed with CH2Cl2 (2×80 mL). The combined organic layers were back-extracted with 1N HCl (60 mL). The combined aqueous HCl layers were cooled in an ice-bath to 2° C., and conc. (37%) HCL (30 mL) was added over 5 minutes. The desired product (bis HCl salt) began to precipitate within 30 minutes. The slurry was stirred 3 hours at 2°-5° C., then the product (bis HCl salt) was collected by filtration and dried in a vacuum oven at 55°-60° C. Yield 11.4 g (68%).

後処理

  1. distillationToluene (100 mL) was distilled out at atmospheric pressure
  2. customthe remaining toluene was removed under vacuum
  3. customto provide a yellow syrup which
  4. custom14 hours
  5. customat -25° C.
  6. temperatureto warm to room temperature
  7. washwashed with CH2Cl2 (2×80 mL)
  8. extractionThe combined organic layers were back-extracted with 1N HCl (60 mL)
  9. temperatureThe combined aqueous HCl layers were cooled in an ice-bath to 2° C.
  10. additionconc. (37%) HCL (30 mL) was added over 5 minutes
  11. customto precipitate within 30 minutes
  12. stirringThe slurry was stirred 3 hours at 2°-5° C.
  13. filtrationthe product (bis HCl salt) was collected by filtration
  14. customdried in a vacuum oven at 55°-60° C

出典と根拠

ORDレコード
ord-3723a041b99f4b28ab43f77971a8f50e
出典データセット
uspto-grants-1997_04
特許番号
US05616720

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