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

HRID 426060ノート

反応式

HRID 426060 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8003Pentane溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-20 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-4d2cd70ae6eb4478ac05fca53901df45
出典データセット
uspto-grants-2012_01
特許番号
US08106221B2

反応ノート

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