Diisopropylamine → methyl 4-(2-tert-butoxy-2-oxoethyl)tetrahydro-2H-pyran-4-carboxylate

HRID 907672

반응식

HRID 907672 반응식
C(NC(C)C)(C)C.C([Li])CCC.[O:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][CH2:14]1.Br[CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26]>O1CCCC1.O>[C:28]([O:27][C:25](=[O:26])[CH2:24][C:16]1([C:19]([O:21][CH3:22])=[O:20])[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1)([CH3:31])([CH3:30])[CH3:29]

참가 물질

7

반응물 4

HCID 7912DiisopropylamineHCID 79177tert-Butyl bromoacetateHCID 27735202H-Pyran-4-carboxylic acid, tetrahydro-, methyl esterHCID 178418339Butyllithium

생성물 1

HCID 21985691methyl 4-(2-tert-butoxy-2-oxoethyl)tetrahydro-2H-pyran-4-carboxylate수율 56.8%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-35 °C

실험 절차

Diisopropylamine (1.28 mL, 9.16 mmol) was diluted with tetrahydrofuran (2 mL) and cooled to −78° C. n-Butyllithium (2.5 M, 3.66 mL, 9.16 mmol) was added dropwise, and the solution was allowed to stir for 1 h. Methyl tetrahydro-2H-pyran-4-carboxylate (1.1 g, 7.63 mmol) was added as a solution in tetrahydrofuran (1.5 mL) at −78° C. The mixture was allowed to warm to −35° C. and stirred for 1 h. tert-Butyl bromoacetate (1.58 mL, 10.7 mmol) was added neat at −35° C. The mixture was allowed to warm to 0° C. and stirred for 2 h. The mixture was stirred at rt overnight. Water was added at 0° C. and the mixture extracted with ethyl acetate. The organic phase was washed with brine, and dried over sodium sulfate. The crude product was purified by flash chromatography (Biotage Flash 40M, 6:1 hexane/ethyl acetate) to afford methyl 4-(2-tert-butoxy-2-oxoethyl)tetrahydro-2H-pyran-4-carboxylate (1.12 g, 56%). LC-MS ret. time 2.47 min, m/z 258.7 (MH+); 1H NMR (300 MHz, CDCl3) δ 1.38 (s, 9H), 1.52-1.61 (m, 2H), 2.00-2.07 (m, 2H), 2.50 (s, 2H), 3.52-3.60 (m, 2H), 3.70 (s, 3H), 3.71-3.77 (m, 2H).

후처리

  1. additionwas added dropwise
  2. additionwas added neat at −35° C
  3. temperatureto warm to 0° C.
  4. stirringstirred for 2 h
  5. stirringThe mixture was stirred at rt overnight
  6. extractionthe mixture extracted with ethyl acetate
  7. washThe organic phase was washed with brine
  8. dry with materialdried over sodium sulfate
  9. customThe crude product was purified by flash chromatography (Biotage Flash 40M, 6:1 hexane/ethyl acetate)

출처 및 근거

ORD 기록
ord-4bd795261eb84f08864cb5e52c242079
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08013166B2

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