Cyclopentanone → Ethyl 3-(cyclopentylamino)-2,2-difluoropropanoate

HRID 914248Notes

Reaction equation

HRID 914248 reaction equation
[NH2:1][CH2:2][C:3]([F:10])([F:9])[C:4]([O:6][CH2:7][CH3:8])=[O:5].[C:11]1(=O)[CH2:15][CH2:14][CH2:13][CH2:12]1.C([O-])(=O)C.[Na+].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(=O)(O)[O-].[Na+]>C1COCC1.C(OCC)(=O)C>[CH:11]1([NH:1][CH2:2][C:3]([F:10])([F:9])[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

8

Reactant 5

HCID 8452CyclopentanoneHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 49853528Ethyl 3-amino-2,2-difluoropropanoate

Product 1

HCID 57634998Ethyl 3-(cyclopentylamino)-2,2-difluoropropanoateYield 84.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl 3-amino-2,2-difluoropropanoate (401 g, 1.5 mol), cyclopentanone (140 mL, 1.575 mol) and sodium acetate (123 g, 1.5 mol) in THF (6.5 L) was added NaBH(OAc)3 (477 g, 2.25 mol) portionwise over a period of 40 min in ice bath. The resulting mixture was stirred vigorously at room temperature overnight. The mixture was added slowly to a stirring solution of ice (3300 mL), saturated aqueous sodium bicarbonate (3300 mL) and ethyl acetate (3300 mL) cooled in ice-salt bath over a period of 30 min. At this time the layers were separated and the pH of aqueous phase was further adjusted to 11 by addition of 25% aqueous NaOH while cooling in the bath. The aqueous phase was extracted with ethyl acetate (3.5 L×2) and all organic layers were combined, washed with cold saturated NaHCO3 (1.5 L×2), brine (1.5 L), dried over MgSO4, filtered and concentrated to give 280 g of ethyl 3-(cyclopentylamino)-2,2-difluoropropanoate.

Workup

  1. customAt this time the layers were separated
  2. additionthe pH of aqueous phase was further adjusted to 11 by addition of 25% aqueous NaOH
  3. temperaturewhile cooling in the bath
  4. extractionThe aqueous phase was extracted with ethyl acetate (3.5 L×2)
  5. washwashed with cold saturated NaHCO3 (1.5 L×2), brine (1.5 L)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e6e77e01d9f74f3ab34f89c55c21594c
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Reaction notes

Loading…