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

HRID 1488639노트

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HRID 1488639 반응식
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

참가 물질

8

반응물 4

HCID 962WaterHCID 66827Phenylboronic AcidHCID 98821474-Nitrophenyl 1,3-thiazol-5-ylmethyl carbonateHCID 228641112S,3S,5S-2,5-Diamino-3-hydroxy-1,6-diphenylhexane, Dihydrochloride

생성물 1

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

시약·촉매·용매 3

HCID 313Hydrochloric Acid용매HCID 1140Toluene용매HCID 6228Dimethylformamide용매2회

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온도
-60 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-7dea39f51f1240a38b036d97a53e1687
출처 데이터셋
uspto-grants-1997_10
특허 번호
US05674882

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