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

HRID 270539Notes

Reaction equation

HRID 270539 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-36c945ce2d8f4054a344ccaba94e0252
Source dataset
uspto-grants-2008_11
Patent number
US07449467B2

Reaction notes

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