Methanol → (1R,4S)-4-[(tert-butoxycarbonyl)amino]-1-ethylcyclopent-2-ene-1-carboxylic acid

HRID 1044616Notes

Reaction equation

HRID 1044616 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([CH2:18][CH3:19])([C:14]([O:16]C)=[O:15])[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.O.O.[OH-].[Li+]>O1CCCC1.CCOC(C)=O>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([CH2:18][CH3:19])([C:14]([OH:16])=[O:15])[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 59833554Methyl(1R,4S)-4-[(tert-Butoxycarbonyl)amino]-1-ethylcyclopent-2-ene-1-carboxylate

Product 1

HCID 59833565(1R,4S)-4-[(tert-butoxycarbonyl)amino]-1-ethylcyclopent-2-ene-1-carboxylic acidYield 31%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl (1R,4S)-4-[(tert-butoxycarbonyl)amino]-1-ethylcyclopent-2-ene-1-carboxylate (4.80 g, 17.8 mmol)) in a mixture of tetrahydrofuran (100 mL), methanol (100 mL) and water (20 mL) was added lithium hydroxide, monohydrate (1.2 g, 28.6 mmol) and the mixture was refluxed overnight. The organic solvents were evaporated. The aqueous layer was then acidified with 6N HCl to about pH 4 and extracted with methylene chloride three times. The combined extracts were dried, filtered, and concentrated to give a mixture of cis/trans isomers (2.93 g, cis/trans=7:1) as a light yellow solid. This solid was dissolved in EtOAc (4.0 mL) with heating and diluted with hexanes (100 mL) to give a clear solution. This solution was allowed to cool to room temperature slowly over 1 h and then maintained at −25° overnight. The cis-isomer was crystallized and dried to provide the desired product (1.40 g, 31%) as a white solid. MS calculated for C13H21NO4: (M+H) 256.2.2; found 156.1 (M+H-Boc).

Workup

  1. temperaturethe mixture was refluxed overnight
  2. customThe organic solvents were evaporated
  3. extractionextracted with methylene chloride three times
  4. customThe combined extracts were dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give
  8. additiona mixture of cis/trans isomers (2.93 g, cis/trans=7:1) as a light yellow solid
  9. temperaturewith heating
  10. customto give a clear solution
  11. temperaturemaintained at −25° overnight
  12. customThe cis-isomer was crystallized
  13. customdried

Sources & evidence

ORD record
ord-d2b47c45df5e48d5ac855f2cedc154ff
Source dataset
uspto-grants-2013_10
Patent number
US08563582B2

Reaction notes

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