Sodium Hydroxide → 1-[[(1,1-dimethylethoxy)carbonyl]amino]cyclopropaneacetic acid

HRID 1485047Notes

Reaction equation

HRID 1485047 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][C:8]1([CH2:11][CH2:12][OH:13])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CC1(C)N([O])C(C)(C)CCC1.P([O-])([O-])([O-])=[O:27].[Na+].[Na+].[Na+].Cl[O-].[Na+].Cl([O-])=O.[Na+].[OH-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C.O>[C:1]([O:5][C:6]([NH:7][C:8]1([CH2:11][C:12]([OH:27])=[O:13])[CH2:9][CH2:10]1)=[O:14])([CH3:4])([CH3:2])[CH3:3]

Participants

10

Reactant 7

HCID 14798Sodium HydroxideHCID 24243Trisodium PhosphateHCID 24477Sodium ThiosulfateHCID 2724126TempoHCID 129931391,1-Dimethylethyl N-[1-(2-hydroxyethyl)cyclopropyl]carbamateHCID 23665760Sodium HypochloriteHCID 23668197Sodium Chlorite

Product 1

HCID 215252351-[[(1,1-dimethylethoxy)carbonyl]amino]cyclopropaneacetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
35 °C

Procedure

To a solution in acetonitrile (275 mL) of the compound (11.1 g) obtained in step (4) above and 2,2,6,6-tetramethylpiperidin-1-oxyl free radical (602 mg), a sodium phosphate buffer (0.67 mol/L, pH 6.7, 206 mL) was added. After heating to 35° C., an aqueous solution of sodium hypochlorite (0.265%, 32.6 mL) and an aqueous solution of sodium chlorite (14.7%, 110 mL) were added simultaneously over a period of 2 hours and the mixture was stirred at that temperature for 55 hours. The mixture was cooled to room temperature and after adding water (400 mL), it was rendered basic with a solution of 2 mol/L sodium hydroxide in water. The reaction mixture was poured into an aqueous solution of sodium thiosulfate (5.75%, 291 mL) at 0° C. After washing with diethyl ether (750 mL), the aqueous layer was added to 2 mol/L hydrochloric acid (140 mL) for pH adjustment to between 2 and 3. The mixture was extracted with diethyl ether and ethyl acetate and the combined organic layers were washed with saturated brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the filtrate was concentrated under reduced pressure. The resulting residue was crystallized with a liquid mixture of n-hexane/ethyl acetate to give {1-[(tert-butoxycarbonyl)amino]cyclopropyl}acetic acid as a colorless solid (9.45 g).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washAfter washing with diethyl ether (750 mL)
  3. additionthe aqueous layer was added to 2 mol/L hydrochloric acid (140 mL) for pH adjustment to between 2 and 3
  4. extractionThe mixture was extracted with diethyl ether and ethyl acetate
  5. washthe combined organic layers were washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe desiccant was removed by filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe resulting residue was crystallized with a liquid mixture of n-hexane/ethyl acetate

Sources & evidence

ORD record
ord-3027b784b06146bebd67b478771852df
Source dataset
uspto-grants-2016_08
Patent number
US09422240B2

Reaction notes

Loading…