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

HRID 1880988Notes

Reaction equation

HRID 1880988 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 the desired product 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-9f0a6d534291449cb902740f9761a93d
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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