Phenylacetyl chloride → (3R,4R)-3-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(methyl-phenylacetyl-amino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158352노트

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HRID 1158352 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][CH3:15])[C@H:10]([CH2:16][N:17]([CH:34]([CH3:36])[CH3:35])[C:18](=[O:33])[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH2:29][CH2:30][O:31][CH3:32])[CH:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:37]1([CH2:43][C:44](Cl)=[O:45])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH3:15])[C:44](=[O:45])[CH2:43][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@H:10]([CH2:16][N:17]([CH:34]([CH3:36])[CH3:35])[C:18](=[O:33])[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH2:29][CH2:30][O:31][CH3:32])[CH:20]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

참가 물질

6

반응물 4

HCID 7679Phenylacetyl chlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 59512501(3R*,4R*)-3-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 59512485(3R,4R)-3-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(methyl-phenylacetyl-amino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

To a solution of (3R,4R)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (2 g, 3.35 mmol) in CH2Cl2 (25 mL), phenylacetyl chloride (0.53 mL, 4.02 mmol) and triethylamine (0.56 mL, 4.02 mmol) are added under N2 atmosphere at 0° C. The mixture is stirred 30 min at 0° C., then allowed to reach RT and further stirred for 1 h. The reaction mixture is diluted with CH2Cl2 and poured into an aqueous saturated solution of NaHCO3. The organic layer is separated, and the aqueous one is extracted twice with CH2Cl2. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude product is purified by flash chromatography on silica gel (eluent: c-hexane/AcOEt 20:80 to 0:100) to give the title compound. TLC, Rf (CH2Cl2/MeOH 95:5)=0.4. MS (LC-MS): 526 [M-Boc+H]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 ml/min): 5.71 min.

후처리

  1. customto reach RT
  2. stirringfurther stirred for 1 h
  3. customThe organic layer is separated
  4. extractionthe aqueous one is extracted twice with CH2Cl2
  5. dry with materialThe combined organic extracts are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified by flash chromatography on silica gel (eluent: c-hexane/AcOEt 20:80 to 0:100)

출처 및 근거

ORD 기록
ord-2818dff2e9f04c91bf8140ae55cd1190
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807709B2

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