N,O-Dimethylhydroxylamine → 4,5-dichloro-2-fluoro-N-methoxy-N-methyl-benzamide

HRID 515085노트

반응식

HRID 515085 반응식
[Cl:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([F:12])[CH:3]=1.CN([C:16]([O:20][N:21]1N=NC2C=CC=N[C:22]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CONC.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)C>[Cl:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([N:21]([O:20][CH3:16])[CH3:22])=[O:7])=[C:4]([F:12])[CH:3]=1

참가 물질

7

반응물 4

HCID 14232N,O-DimethylhydroxylamineHCID 81531DiisopropylethylamineHCID 27740154,5-Dichloro-2-fluorobenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

생성물 1

HCID 903153424,5-dichloro-2-fluoro-N-methoxy-N-methyl-benzamide수율 83%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

실험 절차

4,5-Dichloro-2-fluoro-benzoic acid (50 mg, 0.24 mmol), HATU (100.0 mg, 0.26 mmol) and N-methoxymethanamine (hydrochloric acid) (23.33 mg, 0.24 mmol) were combined in DMF (1.0 mL) and treated with DIEA (83.33 μL, 0.48 mmol). After 10 min, the reaction was complete. The reaction was diluted with diethyl ether and washed with 50% sat. NaHCO3 (2×) and brine, dried over Na2SO4, filtered and concentrated. Silica gel chromatography using a gradient of ethyl acetate/hexanes from 0 to 30% provided 4,5-dichloro-2-fluoro-N-methoxy-N-methyl-benzamide (50 mg, 83%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J=6.3 Hz, 1H), 7.26 (d, J=8.6 Hz, 1H), 3.56 (s, 3H), 3.35 (s, 3H) ppm.

후처리

  1. washwashed with 50% sat. NaHCO3 (2×) and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

출처 및 근거

ORD 기록
ord-1952eaada2ee417185d15f78894012c8
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108903B2

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