Lithium Hydroxide → 4-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(pyridin-3-yl)methyl]pyrrolidin-2-yl}methyl)benzoic acid

HRID 1911835노트

반응식

HRID 1911835 반응식
[OH:1][C@H:2]([C:26]1[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=1)[C@H:3]1[CH2:7][CH2:6][C@@H:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([O:17]C)=[O:16])=[CH:11][CH:10]=2)[N:4]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].[OH-].[Li+]>CO.O.O>[C:22]([O:21][C:19]([N:4]1[C@@H:3]([C@H:2]([OH:1])[C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[CH2:7][CH2:6][C@H:5]1[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]([OH:17])=[O:16])=[CH:13][CH:14]=1)=[O:20])([CH3:25])([CH3:23])[CH3:24]

참가 물질

5

반응물 2

HCID 3939Lithium HydroxideHCID 68396456Tert-butyl (2R,5S)-2-[(R)-hydroxy(pyridin-3-yl)methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate

생성물 1

HCID 679723824-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(pyridin-3-yl)methyl]pyrrolidin-2-yl}methyl)benzoic acid수율 84%

시약·촉매·용매 2

HCID 962Water용매HCID 22242641Methanol--water (1/1)용매

실험 절차

To a stirred solution of the title compound from Step A (8.51 g, 20.0 mmol) in methanol/water=4:1 (50 mL) was added lithium hydroxide (2.39 g, 100 mmol). The resulting mixture was stirred at RT overnight. The mixture was diluted with water and extracted with ether. The aqueous layer was acidified with 1N citric acid to PH 4.5, and then extracted with ethyl acetate. The organic layer was separated and washed with water, brine, dried over Na2SO4, and concentrated. The residue was purified by SFC (using an AD column 35% MeOH/65% CO2, 150 ml/min 100 bar) to afford 6.90 g (84%) of the title compound (i-4) as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.53 (s, 2H), 8.00 (d, J=7.7 Hz, 2H), 7.77 (d, J=6.4 Hz, 1H), 7.32-7.29 (m, 1H), 7.21 (d, J=8.0 Hz, 2H), 5.22 (s, 1H), 4.51 (d, J=8.4 Hz, 1H), 4.13-4.11 (m, 1H), 4.09-4.01 (m, 1H), 3.07-3.04 (m, 1H), 2.58-2.56 (m, 1H), 1.68-1.51 (m, 2H), 1.42 (s, 9H). MS: m/z (EST) 413 (M+1).

후처리

  1. extractionextracted with ether
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with water, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by SFC (

출처 및 근거

ORD 기록
ord-4489810e960848bb95c139ea1fe1faa2
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08604038B2

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