Hydrochloric Acid → tert-Butyl 3-(2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-5-fluorophenyl)-3-oxopropyl(methyl)carbamate

HRID 426060노트

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HRID 426060 반응식
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:10][CH2:11][C:12]([CH3:15])([CH3:14])[N:13]=1.CON(C)[C:19](=[O:31])[CH2:20][CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26].Cl>C1COCC1.CCCCC>[CH3:14][C:12]1([CH3:15])[CH2:11][O:10][C:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[C:19](=[O:31])[CH2:20][CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[N:13]1

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 59364357Tert-butyl 3-(methoxy(methyl)amino)-3-oxopropyl(methyl)carbamateHCID 593643802-(2-Bromo-4-fluorophenyl)-4,4-dimethyl-4,5-dihydrooxazole

생성물 1

HCID 59364358tert-Butyl 3-(2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-5-fluorophenyl)-3-oxopropyl(methyl)carbamate수율 61.4%

시약·촉매·용매 2

HCID 8003Pentane용매HCID 8028Tetrahydrofuran용매2회

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온도
-20 °C

실험 절차

A stirred solution of 2-(2-bromo-4-fluorophenyl)-4,4-dimethyl-4,5-dihydrooxazole (1.2 g, 4.7 mmol) in dry THF (6 mL) was cooled to −78° C. and a solution of tert-buLi (1.7 M in pentane, 5.5 mL, 9.3 mmol) was added drop wise. After 30 min, a solution of tert-butyl 3-(methoxy(methyl)amino)-3-oxopropyl(methyl)carbamate (0.77 g, 3.1 mmol) in dry THF (5 mL) was added. The cooling bath was allowed to warm to −20° C. and the reaction mixture was stirred between −20° C. and 0° C. for 4 h. After warming to room temperature, the mixture was added 0.2N HCl (50 mL). The mixture was extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (120 g column, 0% ethyl acetate in hexanes to 60% ethyl acetate in hexanes) to give product (0.72 g, 61%). 1H NMR (CDCl3) 7.62 (brs, 1H), 6.88 (t, J=7.5 Hz, 1H), 6.79 (brs, 1H), 3.80-4.00 (m, 2H), 3.30 (t, J=7.0 Hz, 2H), 2.76 (brs, 2H), 2.59 (s, 3H), 1.13 (s, 15H); MS EI m/z 379 (M+H)+.

후처리

  1. temperatureAfter warming to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (2×100 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (120 g column, 0% ethyl acetate in hexanes to 60% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-4d2cd70ae6eb4478ac05fca53901df45
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08106221B2

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