Tetrahydrofuran → Methyl 2-(4-chlorophenyl)-3-(2,2,2-trifluoroethylamino)propanoate

HRID 82410Notes

Reaction equation

HRID 82410 reaction equation
Cl.[NH2:2][CH2:3][CH:4]([C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=1)[C:5]([O:7][CH3:8])=[O:6].C1COCC1.CCN(C(C)C)C(C)C.O([CH2:38][C:39]([F:42])([F:41])[F:40])S(C(F)(F)F)(=O)=O>CN(C=O)C>[Cl:15][C:12]1[CH:11]=[CH:10][C:9]([CH:4]([CH2:3][NH:2][CH2:38][C:39]([F:42])([F:41])[F:40])[C:5]([O:7][CH3:8])=[O:6])=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 81531DiisopropylethylamineHCID 66617900Methyl 3-amino-2-(4-chlorophenyl)propanoate hydrochloride

Product 1

HCID 66617993Methyl 2-(4-chlorophenyl)-3-(2,2,2-trifluoroethylamino)propanoateYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of methyl 3-amino-2-(4-chlorophenyl)propanoate hydrochloride (215 mg, 0.86 mmol) in 1:1 THF:DMF (3.0 mL) was treated with DIEA (389 uL, 2.23 mmol) at room temperature. Trifluoroethyl triflate (299 mg, 1.29 mmol) was added to the mixture, and the reaction was stirred for 20 hours to completion. The mixture was partitioned between ethyl acetate and diluted NaHCO3 solution. The aqueous portion was extracted twice, and the combined organics were washed with water (3×). The organic portion was washed with brine, separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography (silica gel eluted with 4:1 hexanes:ethyl acetate, Rf=0.18) to afford the pure methyl 2-(4-chlorophenyl)-3-(2,2,2-trifluoroethylamino)propanoate (235 mg, 93%) as a colorless oil. LCMS (APCI+) m/z 296.0 [M+H]+.

Workup

  1. customThe mixture was partitioned between ethyl acetate and diluted NaHCO3 solution
  2. extractionThe aqueous portion was extracted twice
  3. washthe combined organics were washed with water (3×)
  4. washThe organic portion was washed with brine
  5. customseparated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography (silica gel eluted with 4:1 hexanes:ethyl acetate, Rf=0.18)

Sources & evidence

ORD record
ord-2dcc300255f04441a7d4f16ed7e78572
Source dataset
uspto-grants-2014_09
Patent number
US08846681B2

Reaction notes

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