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

HRID 220719Notes

Reaction equation

HRID 220719 reaction equation
[NH2:1][CH2:2][C:3]([F:9])([F:8])[C:4]([O:6][CH3:7])=[O:5].[C:10]1(=O)[CH2:14][CH2:13][CH2:12][CH2:11]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>CCOC(C)=O.CC(O)=O.C1COCC1>[CH:10]1([NH:1][CH2:2][C:3]([F:9])([F:8])[C:4]([O:6][CH3:7])=[O:5])[CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 8452CyclopentanoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 22635306HCID 22635306, compound

Product 1

HCID 67117821Methyl 3-(cyclopentylamino)-2,2-difluoropropanoateYield 60%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask was added methyl 3-amino-2,2-difluoropropanoate (570 mg, 3.24 mmol), THF (20 mL), cyclopentanone (0.433 mL, 4.87 mmol), and HOAc (1 mL). To this mixture was added sodium triacetoxyborohydride (1.06 g, 5 mmol) portionwise. The reaction was left to stir overnight. It was then added slowly to a stirring solution of ice, NaHCO3 (sat.), and EtOAc. The aqueous layer was further extracted with EtOAc, the organic extracts combined, dried over MgSO4, filtered and concentrated to yield methyl 3-(cyclopentylamino)-2,2-difluoropropanoate as clear syrup (400 mg, 60%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.30 (td, J=13, 6 Hz, 2 H) 1.43 (d, J=8 Hz, 1 H) 1.47-1.70 (m, 4 H) 1.77 (dt, J=12, 6 Hz, 2 H) 3.12 (t, J=6 Hz, 1 H) 3.19 (t, J=14 Hz, 2 H) 3.88 (s, 3 H).

Workup

  1. waitThe reaction was left
  2. extractionThe aqueous layer was further extracted with EtOAc
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-a4a4a8994cb5495da83e0221312b0bb5
Source dataset
uspto-grants-2012_06
Patent number
US08202990B2

Reaction notes

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