Ethyl Acetate → (3R,4S)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-((S)-1-phenyl-propylcarbamoyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158431

반응식

HRID 1158431 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][OH:35])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1([C@@H:42]([N:45]=[C:46]=[O:47])[CH2:43][CH3:44])C=CC=CC=1.[Al+3].[Cl-].[Cl-].[Cl-].CCO[C:55]([CH3:57])=O>CCOCC>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([C@H:34]([O:35][C:46](=[O:47])[NH:45][CH2:42][CH2:43][CH3:44])[C:57]2[CH:55]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C@H:11]([CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 6451240Aluminum(III) Chloride2회HCID 7018275[(1S)-1-isocyanatopropyl]benzene2회HCID 59512299(3S,4R)-3-Hydroxymethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 68617439(3R,4S)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-((S)-1-phenyl-propylcarbamoyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 3283Diethyl Ether용매

실험 절차

To a solution of (3S,4R)-3-hydroxymethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, 0.404 mmol) in ether (12 mL) are successively added (S)-1-phenylpropyl isocyanate (130.4 mg, 0.809 mmol) and AlCl3 (54 mg, 0.404 mmol). The mixture is stirred at RT under nitrogen overnight. (S)-1-phenylpropyl isocyanate (150 μL) and AlCl3 (54 mg, 0.404 mmol) are again added and the mixture further stirred for 5 h. AcOEt is added and the reaction mixture quenched by the addition of an aqueous saturated solution of NaHCO3. The layers are separated and the aqueous one back extracted twice with AcOEt. The combined organic extracts are dried over Na2SO4, filtered and concentrated under reduced pressure. The crude mixture is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 95:5) to give the title product TLC, Rf (CH2Cl2/MeOH 95:5)=0.35. MS (LC-MS): 656.2 [M+H]+; tR (HPLC, Nucleosil C18-HD column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/1.5 min, flow: 1 ml/min): 3.94 min.

후처리

  1. stirringthe mixture further stirred for 5 h
  2. customthe reaction mixture quenched by the addition of an aqueous saturated solution of NaHCO3
  3. customThe layers are separated
  4. extractionthe aqueous one back extracted twice with AcOEt
  5. dry with materialThe combined organic extracts are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude mixture is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 95:5)

출처 및 근거

ORD 기록
ord-72a18a1da1d94972b772a9206006d253
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807709B2

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