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

HRID 1911833Notes

Reaction equation

HRID 1911833 reaction equation
[Si:1]([O:8][C@H:9]([C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1)[C@H:10]1[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([O:24]C)=[O:23])=[CH:18][CH:17]=2)[N:11]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH-].[Li+]>CO.O.O>[C:29]([O:28][C:26]([N:11]1[C@@H:10]([C@H:9]([O:8][Si:1]([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:3])[CH3:2])[C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)[CH2:14][CH2:13][C@H:12]1[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]([OH:24])=[O:23])=[CH:20][CH:21]=1)=[O:27])([CH3:30])([CH3:31])[CH3:32]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86666749Tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(pyridin-3-yl)methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate

Product 1

HCID 679717394-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(pyridin-3-yl)methyl]pyrrolidin-2-yl}methyl)benzoic acidYield 74%

Reagents, catalysts & solvents 2

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

Procedure

To a stirred solution of the title compound from Step D (2.5 g, 4.6 mmol) in methanol/water 4:1 (30 mL) was added lithium hydroxide (533 mg, 23.1 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 reverse phase HPLC (Luna10u, 250×50 mm I.D.; 45-65% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient) to afford 1.31 g (74%) of the title compound (i-3) as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.64 (s, 2H), 7.93 (d, J=7.8 Hz, 2H), 7.80 (s, 1H), 7.44-7.38 (m, 1H), 7.03 (s, 2H), 5.66-5.33 (m, 1H), 4.16 (s, 1H), 4.00-3.88 (m, 1H), 3.01-2.95 (m, 1H), 2.68-1.58 (m, 1H), 2.04-1.83 (m, 2H), 1.60 (s, 9H), 1.31-1.20 (m, 2H), 0.96 (s, 9H), 0.17 (s, 3H), 0.00 (s, 3H). MS: m/z (ESI) 527 (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 reverse phase HPLC (Luna10u, 250×50 mm I.D.; 45-65% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient)

Sources & evidence

ORD record
ord-9e7e776b84a14e7fa0ebc8be4921bf66
Source dataset
uspto-grants-2013_12
Patent number
US08604038B2

Reaction notes

Loading…