Dimethylformamide → N-Methoxy-N-methyl-4-(5-trifluoromethyl-isoxazol-3-yl)-benzamide

HRID 1514084Notes

Reaction equation

HRID 1514084 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH:4]=1.Cl.NO.C([N:24]([CH2:27]C)CC)C.C1CCC(N=C=NC2CCCCC2)CC1.CN([CH:47]=[O:48])C>ClCCl.CN(C1C=CN=CC=1)C>[CH3:47][O:48][N:24]([CH3:27])[C:12](=[O:14])[C:11]1[CH:10]=[CH:9][C:8]([C:5]2[CH:4]=[C:3]([C:2]([F:1])([F:18])[F:17])[O:7][N:6]=2)=[CH:16][CH:15]=1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 443297Hydroxyamine hydrochlorideHCID 576061124-(5-(Trifluoromethyl)isoxazol-3-yl)benzoic acid

Product 1

HCID 57606119N-Methoxy-N-methyl-4-(5-trifluoromethyl-isoxazol-3-yl)-benzamideYield 74%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(5-Trifluoromethyl-isoxazol-3-yl)-benzoic acid (Preparative Example 11, 1.024 g, 4.0 mmol) in dichloromethane (14 mL) at 0-5° C. was treated with DMF (2 mL) followed by DMAP (50 mg), hydroxylamine hydrochloride (468 mg, 4.8 mmol), triethylamine (458 μL, 4.8 mmol), and DCC (990 mg, 4.8 mmol). The reaction was allowed to warm to room temperature and stirred 16 hr then evaporated in vacuo. The crude material was then chromatographed on silica gel with EtOAc/hexanes (40%) as eluant to afford product as a colorless solid (890 mg, 74%). 1H NMR (CDCl3) 3.40 (s, 3 H), 3.57 (s, 3 H), 7.06 (s, 3), 7.82 (d, J=8.3, 2 H), 7.88 (d, J=8.8, 2 H). 13C NMR 33.7, 61.4, 103.7, 118.0 (q, J=460), 127.1, 129.3, 129.4, 136.6, 159.7 (q, J=42), 162.2, 169.0. 19F NMR −64.6. LC/MS 6.01 min, [M+1]+ 301.

Workup

  1. customthen evaporated in vacuo
  2. customThe crude material was then chromatographed on silica gel with EtOAc/hexanes (40%) as eluant

Sources & evidence

ORD record
ord-6313a71c085646f9859303f6037d7fec
Source dataset
uspto-grants-2012_07
Patent number
US08222243B2

Reaction notes

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