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

HRID 1804580Notes

Reaction equation

HRID 1804580 reaction equation
[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]

Participants

5

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

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 (ESI) 413 (M+1).

Workup

  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 (

Sources & evidence

ORD record
ord-fae70953464a44bd9d8655c7691439e6
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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