Lithium Hydroxide → 1-(Tert-butoxycarbonylamino-methyl)-2-isobutyl-cyclopropanecarboxylic acid

HRID 1297236Notes

Reaction equation

HRID 1297236 reaction equation
C[O:2][C:3]([C:5]1([CH2:12][NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7][CH:6]1[CH2:8][CH:9]([CH3:11])[CH3:10])=[O:4].[Li+].[OH-]>CO.O>[C:17]([O:16][C:14]([NH:13][CH2:12][C:5]1([C:3]([OH:4])=[O:2])[CH2:7][CH:6]1[CH2:8][CH:9]([CH3:10])[CH3:11])=[O:15])([CH3:18])([CH3:20])[CH3:19]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 695157781-(Tert-butoxycarbonylamino-methyl)-2-isobutyl-cyclopropanecarboxylic acid methyl ester

Product 1

HCID 221827451-(Tert-butoxycarbonylamino-methyl)-2-isobutyl-cyclopropanecarboxylic acidYield 97%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 1-(tert-butoxycarbonylamino-methyl)-2-isobutyl-cyclopropanecarboxylic acid methyl ester (9.1 g, 31.9 mmol) in MeOH (260 mL) was added a solution of LiOH (3.34 g, 79.7 mmol) in water (80 mL). The reaction mixture was heated to reflux for 3 hours and cooled to room temperature. Excess of solvent was removed and the residue was dissolved in water (100 mL). The aqueous solution was washed with ether, acidified to pH=3 with 2N HCl and extracted with EtOAc (2×150 mL). The combined organic phase was washed with brine, dried (Na2SO4) and evaporation of the solvent gave 8.4 g (97%) of 1-(tert-butoxycarbonylamino-methyl)-2-isobutyl-cyclopropanecarboxylic acid as a colorless oil: 1H NMR (300 MHz, CD3OD) δ 0.71 (dd, J=4.0, 6.4 Hz, 1H), 0.95 (t, J=6.4 Hz, 6H), 1.35 (m, 1H), 1.43 (s, 1H), 1.49-1.55 (m, 1H), 1.64-1.69-(m, 2H) 3.23 (d, J=14.2 Hz, 1H), 3.40 (d, J=14.2 Hz, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 3 hours
  3. customExcess of solvent was removed
  4. dissolutionthe residue was dissolved in water (100 mL)
  5. washThe aqueous solution was washed with ether
  6. extractionextracted with EtOAc (2×150 mL)
  7. washThe combined organic phase was washed with brine
  8. customdried
  9. custom(Na2SO4) and evaporation of the solvent

Sources & evidence

ORD record
ord-1c46dc8d823d43d792967315f0903e2a
Source dataset
uspto-grants-2007_07
Patent number
US07250433B2

Reaction notes

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