Methanol → (2S,4R)-1-((2S,3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid

HRID 523192Notes

Reaction equation

HRID 523192 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:22]([CH2:30][CH3:31])[CH2:23][CH:24]([CH3:29])[CH2:25][CH2:26][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].O.[Li+].[OH-].CO>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:22]([CH2:30][CH3:31])[CH2:23][CH:24]([CH3:29])[CH2:25][CH2:26][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

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 86683260(2S,4R)-methyl 1-((2S,3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate

Product 1

HCID 86683262(2S,4R)-1-((2S,3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acidYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2S,4R)-methyl 1-((2S,3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (1.5 g, 3.40 mmole) in THF:water (16 mL, 1:1) was added LiOH (286 mg, 6.80 mmole) followed by 3 mL of methanol at room temperature. The reaction mass was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and the residue was diluted with water and acidified with aqueous 1.5 N HCl solutions. The aqueous solution was extracted with ethyl acetate (20 mL×3). The combined organic layers were dried over anhydrous Na2SO4; filtered; then concentrated under reduced pressure to afford (2S,4R)-1-((2S,3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid (1.3 g, 90%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 0.81-0.93 (m, 6H), 1.12-1.29 (m, 5H), 1.30-1.50 (m, 11H), 1.71-1.80 (m, 2H), 1.91-2.51 (m, 4H), 3.57-3.59 (m, 1H), 4.27-4.35 (m, 3H), 4.92-4.97 (m, 2H), 5.01-5.15 (m, 1H), 5.74-5.79 (m, 1H), 6.30-6.80 (m, 1H), 12.50 (sb, 1H). MS: MS m/z 427.6 (M++1).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. additionthe residue was diluted with water
  3. extractionThe aqueous solution was extracted with ethyl acetate (20 mL×3)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationthen concentrated under reduced pressure

Sources & evidence

ORD record
ord-a349da3c0cef4146be4629af0b53d071
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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