Lithium Hydroxide → (1R,2S)-1-(((1,1-Dimethylethoxy)carbonyl)amino)-2-ethenylcyclopropanecarboxylic acid

HRID 2252622Notes

Reaction equation

HRID 2252622 reaction equation
C([O:3][C:4]([C@@:6]1([NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C@H:7]1[CH:9]=[CH2:10])=[O:5])C.[Li+].[OH-]>C1COCC1.CO.O>[C:15]([O:14][C:12]([NH:11][C@:6]1([C:4]([OH:5])=[O:3])[CH2:8][C@H:7]1[CH:9]=[CH2:10])=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 10658673Ethyl (1R,2S)-1-[[(1,1-dimethylethoxy)carbonyl]amino]-2-ethenylcyclopropanecarboxylate

Product 1

HCID 10376443(1R,2S)-1-(((1,1-Dimethylethoxy)carbonyl)amino)-2-ethenylcyclopropanecarboxylic acidYield 87.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1(R)-tert-butoxycarbonylamino-2(S)-vinyl-cyclopropanecarboxylic acid ethyl ester (3.28 g, 13.2 mmol) in THF (7 mL) and methanol (7 mL) was added a suspension of LiOH (1.27 g, 53.0 mmol) in water (14 mL). The mixture was stirred overnight at room temperature and quenched with 1N NaOH (15 mL) and water (20 mL). The resulting mixture was washed with ethyl acetate (20 mL), and the organic phase was extracted with 20 mL 0.5N NaOH. The combined aqueous phases were acidified with 1N HCl until pH 4 and extracted with ethyl acetate (3×40 mL). The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated to yield the title compound as a white solid (2.62 g, 87%). 1H NMR: (DMSO-d6) δ 1.22-1.26 (m, 1H), 1.37 (s, 9H), 1.50-1.52 (m, 1H), 2.05 (q, J=9 Hz, 1H), 5.04 (d, J=10 Hz, 1H), 5.22 (d, J=17 Hz, 1H), 5.64-5.71 (m, 1H), 7.18, 7.53 (s, NH (rotamers), 12.4 (br s, 1H)); LC-MS (retention time: 1.67 minutes, method B), MS m/z 228 (M++H).

Workup

  1. customquenched with 1N NaOH (15 mL) and water (20 mL)
  2. washThe resulting mixture was washed with ethyl acetate (20 mL)
  3. extractionthe organic phase was extracted with 20 mL 0.5N NaOH
  4. extractionextracted with ethyl acetate (3×40 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-60e3e21a91464cc599bdb3f8e223ada7
Source dataset
uspto-grants-2008_01
Patent number
US07323447B2

Reaction notes

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