Lithium hydroxide, monohydrate → (1S,4S)-4-((tert-butoxycarbonyl)amino)-1-isopropylcyclopent-2-enecarboxylic acid

HRID 1044552Notes

Reaction equation

HRID 1044552 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([CH:18]([CH3:20])[CH3:19])([C:14]([O:16]C)=[O:15])[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>C1COCC1.CO.O>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([CH:18]([CH3:20])[CH3:19])([C:14]([OH:16])=[O:15])[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 60122269Methyl(1S,4S)-4-[(tert-Butoxycarbonyl)amino]-1-isopropylcyclopent-2-ene-1-carboxylate

Product 1

HCID 60122256(1S,4S)-4-((tert-butoxycarbonyl)amino)-1-isopropylcyclopent-2-enecarboxylic acidYield 97.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl (1S,4S)-4-[(tert-butoxycarbonyl)amino]-1-isopropylcyclopent-2-ene-1-carboxylate (18.42 g, 65 mmol) in THF (500 mL), methanol (500 mL) and water (100 mL) was added lithium hydroxide monohydrate (5.00 g, 119 mmol). The mixture was heated to reflux overnight. After 18 hours, TLC indicated a very trace amount of starting material. The organic solvents were removed in vacuo and the aqueous layer was extracted with ether (200 mL) to remove the unreacted starting material. The aqueous layer was acidified with concentrated HCl to pH=4 while being cooled in an ice bath. The resulting solution was extracted with methylene chloride three times. The extracts were dried over MgSO4 and concentrated to give a solid (17 g). The solid was dissolved in hot ethyl acetate (22 mL) and hexanes (550 mL) were added to the solution. The solution was slowly cooled down to room temperature before putting into a freezer reading at −22 to −24° C. After two days, the crystals were removed off and the liquid was evaporated in vacuo to give the desired product as a white foamy solid (9.78 g, 56%). MS calculated for C14H23NO4: (M+H)+ 270; found 170.1 (M-Boc+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. customThe organic solvents were removed in vacuo
  4. extractionthe aqueous layer was extracted with ether (200 mL)
  5. customto remove the
  6. temperaturewhile being cooled in an ice bath
  7. extractionThe resulting solution was extracted with methylene chloride three times
  8. dry with materialThe extracts were dried over MgSO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-39d2c335a0264426825623501f4a713c
Source dataset
uspto-grants-2013_10
Patent number
US08563582B2

Reaction notes

Loading…