Water → tert-butyl(R)-3-[chlorocarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino]pyrrolidine-1-carboxylate

HRID 409601

반응식

HRID 409601 반응식
[Cl:1][C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[C:13]1([CH:23]([NH:25][C@@H:26]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27]2)[CH3:24])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C.O>C(Cl)Cl>[Cl:1][C:2]([N:25]([C@@H:23]([C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1)[CH3:24])[C@H:26]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[O:32])[CH2:27]1)=[O:4].[Cl:1][C:2]([N:25]([C@@H:23]([C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1)[CH3:24])[C@@H:26]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[O:32])[CH2:27]1)=[O:4]

참가 물질

7

반응물 4

HCID 962WaterHCID 8471TriethylamineHCID 94429Triphosgene2회HCID 67406775tert-butyl(R)-3-[1-(naphthalen-1-yl)ethylamino]pyrrolidine-1-carboxylate

생성물 2

HCID 58973521tert-butyl(R)-3-[chlorocarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino]pyrrolidine-1-carboxylateHCID 58973541tert-butyl(S)-3-[chlorocarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino]pyrrolidine-1-carboxylate

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 14.9 g of triphosgene dissolved in 400 ml of methylene chloride was added dropwise a solution containing 25.68 g of tert-butyl (R)-3-[1-(naphthalen-1-yl)ethylamino]pyrrolidine-1-carboxylate (the compound obtained in the above-mentioned Reference example 1.005 (1)) and 31.5 ml of triethylamine in 100 ml of methylene chloride at −20° C. Further, 7.5 g of triphosgene was added to the same, and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction mixture, the mixture was stirred and the liquids were separated. The organic layer was dried, the solvent was evaporated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=6:1→2:1) to obtain 10.63 g of tert-butyl (S)-3-[chlorocarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino]pyrrolidine-1-carboxylate and 9.22 g of tert-butyl (R)-3-[chlorocarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino]pyrrolidine-1-carboxylate shown in the following Reference example Table, respectively. (2) To 18.52 g of tert-butyl (S)-3-[chlorocarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino]pyrrolidine-1-carboxylate was added 1.0 liter of tert-butanol, and the mixture was stirred at 60° C. for 2 days. The reaction mixture was concentrated, and then, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain 9.24 g of tert-butyl (S)-3-[tert-butoxycarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino)]pyrrolidine-1-carboxylate (the following Reference example 1.006(a)).

후처리

  1. additionwas added dropwise a solution
  2. customat −20° C
  3. stirringthe mixture was stirred
  4. customthe liquids were separated
  5. customThe organic layer was dried
  6. customthe solvent was evaporated
  7. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=6:1→2:1)

출처 및 근거

ORD 기록
ord-6f0673c2763347f6a22791aa0846e607
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759387B2

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