Isobutyl chloroformate → 5-bromo-N-methoxy-N-methyl-1-naphthamide

HRID 661860

반응식

HRID 661860 반응식
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]([OH:14])=O.ClC(OCC(C)C)=O.Cl.[CH3:24][NH:25][O:26][CH3:27]>C1COCC1.O>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]([N:25]([O:26][CH3:27])[CH3:24])=[O:14]

참가 물질

6

반응물 3

HCID 62365Isobutyl chloroformateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 6976055-Bromonaphthalene-1-carboxylic acid

생성물 1

HCID 586786355-bromo-N-methoxy-N-methyl-1-naphthamide수율 30%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

Step 1 A solution of 5-bromo-1-naphthoic acid (prepared according to the procedure of Hausamann, Chem. Ber., 1876, 9, 1519; 2.00 g, 7.97 mmol) in THF (50 mL) was treated with TEA (2.22 mL, 15.93 mmol), then with isobutyl chloroformate (1.088 g, 7.97 mmol) and the resulting suspension was stirred at rt. After 25 min, the mixture was treated with additional TEA (2.22 mL, 15.93 mmol), then with a solution of N,O-dimethylhydroxylamine hydrochloric acid salt (0.777 g, 7.97 mmol) in water (5 mL), and the mixture was stirred at rt. After 2.5 h, the mixture was concentrated and the residue was taken up in EtOAc and water. The mixture was filtered, the layers were separated, and the organic phase was washed with NaHCO3 (aq), dried and concentrated to provide 5-bromo-N-methoxy-N-methyl-1-naphthamide as a pasty solid (1.03 g, 30%) contaminated with ca. 30% isobutyl 5-bromo-1-naphthoate. Mass spectrum m/z 294, 296 (M+H)+. Without further purification, a solution of this material (1.01 g, 2.404 mmol) in THF (15 mL) was stirred on ice and treated with (4-fluorophenyl)magnesium bromide, 2M in ether (7.21 mL, 14.42 mmol). The solution was stirred on ice and allowed to slowly warm to rt. After 16 h, the mixture was treated with 1 M hydrochloric acid and extracted twice with EtOAc. The combined organic layers were dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from hexane to 85:15 hexane-EtOAc) to provide (5-bromonaphthalen-1-yl)(4-fluorophenyl)methanone as a pale yellow viscous oil (658 mg, 83%). 1H NMR (400 MHz, methanol-d4) δ 8.49 (1H, d, J=8.6 Hz), 7.95 (1H, d, J=8.6 Hz), 7.86-7.93 (3H, m), 7.74 (1H, dd, J=8.5, 7.2 Hz), 7.64-7.68 (1H, m), 7.40 (1H, dd, J=8.5, 7.6 Hz), 7.25 (2H, t, J=8.8 Hz). Mass spectrum m/z 329, 331 (M+H)+.

후처리

  1. waitAfter 2.5 h
  2. concentrationthe mixture was concentrated
  3. filtrationThe mixture was filtered
  4. customthe layers were separated
  5. washthe organic phase was washed with NaHCO3 (aq)
  6. customdried
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-e66b1a3152574017b75ac822ac2480ab
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084620B2

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