Methyl chloroformate → Tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-((methoxycarbonyl)oxy)piperidine-1-carboxylate

HRID 514848노트

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HRID 514848 반응식
[Si:1]([O:8][CH2:9][C:10]#[C:11][C:12]1([OH:25])[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li]CCCC.[C:31](Cl)(=[O:34])[O:32][CH3:33]>C1COCC1>[C:21]([O:20][C:18]([N:15]1[CH2:16][CH2:17][C:12]([C:11]#[C:10][CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])([O:25][C:31]([O:32][CH3:33])=[O:34])[CH2:13][CH2:14]1)=[O:19])([CH3:24])([CH3:23])[CH3:22]

참가 물질

5

반응물 3

HCID 6586Methyl chloroformateHCID 90418995Tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-hydroxypiperidine-1-carboxylateHCID 178418339Butyllithium

생성물 1

HCID 90418921Tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-((methoxycarbonyl)oxy)piperidine-1-carboxylate수율 78.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

To a solution of tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-hydroxypiperidine-1-carboxylate (500 mg, 1.353 mmol) in 30 mL of anhydrous THF was added dropwise n-BuLi (0.65 mL, 1.623 mmol) at −78° C. under N2. After stirring for 1 h at −78° C., methyl carbonochloridate (176.2 mg, 1.623 mmol) in THF (1 mL) was added dropwise to the above solution at −78° C. under N2. The resulting mixture was stirred at −78° C. under N2 for 2 h, then allowed to warm to r.t. and stirred for another 8 h. The reaction mixture was cooled to −78° C. and quenched by sat. NH4Cl aq., and the resulting mixture was extracted with EtOAc (50 mL, 30 mL). The combined organic phase was washed with brine, dried over anhy. Na2SO4 and concentrated in vacuo. Column chromatography (15% PE/EtOAc) afforded 453 mg of title compound. 1H NMR (CHLOROFORM-d) δ: 4.40 (s, 2H), 4.26-4.15 (m, 2H), 3.80-3.67 (m, 2H), 3.41-3.28 (m, 2H), 2.27-2.14 (m, 2H), 2.00 (ddd, J=13.1, 9.2, 3.9 Hz, 2H), 1.48 (s, 9H), 1.33 (t, J=7.1 Hz, 4H), 0.92 (s, 9H), 0.14 (s, 6H).

후처리

  1. stirringThe resulting mixture was stirred at −78° C. under N2 for 2 h
  2. temperatureto warm to r.t.
  3. stirringstirred for another 8 h
  4. temperatureThe reaction mixture was cooled to −78° C.
  5. customquenched by sat. NH4Cl aq.
  6. extractionthe resulting mixture was extracted with EtOAc (50 mL, 30 mL)
  7. washThe combined organic phase was washed with brine
  8. customdried over anhy
  9. concentrationNa2SO4 and concentrated in vacuo

출처 및 근거

ORD 기록
ord-f385807448fe4a8fa8193f0f95439f87
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108921B2

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