Sodium Hydroxide → 4-{[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]methyl}benzoic acid

HRID 732693노트

반응식

HRID 732693 반응식
[C:1]([O:5][C:6]([N:8]([CH2:21][C@@H:22]1[C@@H:26]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:25][N:24]([CH2:33][C:34]2[CH:43]=[CH:42][C:37]([C:38]([O:40]C)=[O:39])=[CH:36][CH:35]=2)[CH2:23]1)[C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO>[C:1]([O:5][C:6]([N:8]([CH2:21][C@@H:22]1[C@@H:26]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:25][N:24]([CH2:33][C:34]2[CH:43]=[CH:42][C:37]([C:38]([OH:40])=[O:39])=[CH:36][CH:35]=2)[CH2:23]1)[C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

4

반응물 2

HCID 14798Sodium HydroxideHCID 68913897methyl 4-{[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]methyl}benzoate

생성물 1

HCID 689138414-{[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]methyl}benzoic acid

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A 170 mg portion of methyl 4-{[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]methyl}benzoate was dissolved in 4 ml of methanol, mixed with 2 ml of 1 M sodium hydroxide aqueous solution at room temperature and stirred for 41Hours. The reaction solution was concentrated under a reduced pressure, and 1 M hydrochloric acid was added to the residue until its pH became 3. This was extracted with chloroform and washed with saturated brine, and then the organic layer was dried with anhydrous sodium sulfate and concentrated under a reduced pressure to obtain 4-{[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]methyl}benzoic acid as a crude product. The thus obtained crude product was dissolved in 3.0 ml of 4 M hydrogen chloride/1,4-dioxane solution and 30 ml of dioxane at room temperature and stirred for 1Hour. The thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol), and then dissolved in 2.0 ml of dioxane, mixed with 2.0 ml of 4 M hydrogen chloride/1,4-dioxane solution and concentrated under a reduced pressure. The residue was dissolved in chloroform and mixed with diisopropyl ether, and the resulting precipitate was collected by filtration and dried under a reduced pressure to obtain 76 mg of 4-{[(3S,4S)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]methyl}benzoic acid dihydrochloride as a colorless solid.

후처리

  1. concentrationThe reaction solution was concentrated under a reduced pressure, and 1 M hydrochloric acid
  2. additionwas added to the residue until its pH
  3. extractionThis was extracted with chloroform
  4. washwashed with saturated brine
  5. dry with materialthe organic layer was dried with anhydrous sodium sulfate
  6. concentrationconcentrated under a reduced pressure

출처 및 근거

ORD 기록
ord-f98f7333b4064f739a4e042227f3899c
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07585886B2

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