Methanol → HCID 86685805, compound

HRID 2361592Notes

Reaction equation

HRID 2361592 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:22]([CH3:30])[CH2:23][CH2:24][CH2:25][CH:26]([CH3:29])[CH:27]=[CH2:28])[C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18]([O:20]C)=[O:19])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.[Li+].[OH-]>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:22]([CH3:30])[CH2:23][CH2:24][CH2:25][CH:26]([CH3:29])[CH:27]=[CH2:28])[C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18]([OH:20])=[O:19])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 86685806HCID 86685806, compound

Product 1

HCID 86685805HCID 86685805, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of (2S,4R)-methyl 1-((2S,3R)-2-(tert-butoxycarbonylamino)-3,7-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (4.3 g, 10 mmol) in THF/water (30 mL, 1:1) was added methanol (10 mL) followed by LiOH (1.3 g, 0.030 moles) at room temperature. The reaction mass was stirred at room temperature overnight. Solvent was evaporated under reduced pressure and the residue was diluted with water (100 mL). The aqueous solution was acidified with aqueous 1.5 N HCl solutions to pH˜3 and extracted with ethyl acetate (100 mL×3). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduce pressure to get the desired product (2S,4R)-((2S,3R)-2-(tert-butoxycarbonylamino)-3,7-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid (3.2 g, 78% yield) as a white solid. 1H NMR (400 MHz, CDCl3): δ ppm 5.70-5.61 (m, 1H), 5.14-5.12 (d, J=8.8 Hz, 1H), 4.96-4.88 (m, 2H), 4.82-4.78 (t, J=8.4 Hz, 1H), 4.52 (bs, 1H), 4.27-4.23 (m, 1H), 3.57-3.53 (m, 3H), 2.48-2.42 (m, 1H), 2.33-2.28 (m, 1H), 1.88-1.82 (m, 2H), 1.45-1.42 (s, 9H), 1.29-1.21 (m, 3H), 0.98-0.93 (m, 7H) MS: MS m/z 411.2 (M++1).

Workup

  1. customSolvent was evaporated under reduced pressure
  2. additionthe residue was diluted with water (100 mL)
  3. extractionextracted with ethyl acetate (100 mL×3)
  4. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-ac691d3661474be080175d865fb11fc0
Source dataset
uspto-grants-2014_04
Patent number
US08691757B2

Reaction notes

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