Lithium Hydroxide → (1R,2S)-ethyl 1-(tert-butoxycarbonylamino)-2-cyclopropylcyclopropanecarboxylate

HRID 1697885Notes

Reaction equation

HRID 1697885 reaction equation
[CH2:1]([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])[CH3:2].[Li+].[OH-].[OH-].[Na+].[C:23](OCC)(=O)C>C1COCC1.CO.O>[CH2:1]([O:3][C:4]([C@@:6]1([NH:11][C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])[CH2:8][C@H:7]1[CH:9]1[CH2:23][CH2:10]1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 10658673Ethyl (1R,2S)-1-[[(1,1-dimethylethoxy)carbonyl]amino]-2-ethenylcyclopropanecarboxylate

Product 1

HCID 59990838(1R,2S)-ethyl 1-(tert-butoxycarbonylamino)-2-cyclopropylcyclopropanecarboxylateYield 87%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 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. To the mixture was added 1.0M NaOH (15 mL), water (20 mL) and ethyl acetate (20 mL). The mixture was shaken, the phases were separated, and the organic phase was again extracted with 20 mL 0.5M NaOH. The combined aqueous phases were acidified with 1.0M HCl until pH=4 and extracted with ethyl acetate (3×40 mL). The combined organic extracts were washed with brine, dried (MgSO4), and filtered to provide the desired product as a white solid (2.62 g, 87%). 1H NMR: (DMSO-d6) δ1.22-1.26 (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 MS m/z 228 (M++H).

Workup

  1. stirringThe mixture was shaken
  2. customthe phases were separated
  3. extractionthe organic phase was again extracted with 20 mL 0.5M 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

Sources & evidence

ORD record
ord-ee8b5e2945d3478b9f370dc9bc0c4e6b
Source dataset
uspto-grants-2012_04
Patent number
US08163921B2

Reaction notes

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