Hydrochloric Acid → N-Methoxy-N-methyl-2-(2,3,5-trifluorophenyl)acetamide

HRID 706387Notes

Reaction equation

HRID 706387 reaction equation
Cl.[F:2][C:3]1[C:8]([F:9])=[CH:7][C:6]([F:10])=[CH:5][C:4]=1[CH2:11][C:12]([OH:14])=O.C1N=CN(C([N:22]2[CH:26]=NC=C2)=O)C=1.C1C[O:30][CH2:29]C1>O>[CH3:29][O:30][N:22]([CH3:26])[C:12](=[O:14])[CH2:11][C:4]1[CH:5]=[C:6]([F:10])[CH:7]=[C:8]([F:9])[C:3]=1[F:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 682631,1'-CarbonyldiimidazoleHCID 27779462,3,5-Trifluorophenylacetic acid

Product 1

HCID 89814700N-Methoxy-N-methyl-2-(2,3,5-trifluorophenyl)acetamideYield 80%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of NHMe(OMe).HCl (20.3 g, 0.21 mol) in THF (110 mL), H2O (40 mL) and TEA (26.3 g, 0.22 mol) was added 2,3,5-trifluorophenylacetic acid (42, 24.7 g, 0.13 mol) and CDI (24.3 g, 0.15 mol) at 0-10° C. The reaction mixture was stirred at 0-10° C. for 5 h. After HPLC showed that the reaction was complete, the mixture was filtered through celite and the filtrate was partitioned with water and EtOAc. The organic solution was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (5-10% EtOAc/PE) to give 43 (24.0 g, 80% yield). 1H NMR (CDCl3, 400 MHz): δ 6.76-6.72 (m, 2H), 3.72 (m, 2H), 3.66 (d, 3H), 3.15 (d, 3H); MS (ESI) m/e [M+H]+: 234.07.

Workup

  1. filtrationthe mixture was filtered through celite
  2. customthe filtrate was partitioned with water and EtOAc
  3. dry with materialThe organic solution was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude residual was further purified by flash chromatography on silica gel (5-10% EtOAc/PE)

Sources & evidence

ORD record
ord-c800d2e478394647a05aafb45cfaf957
Source dataset
uspto-grants-2015_11
Patent number
US09174989B2

Reaction notes

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