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

HRID 2202384ノート

反応式

HRID 2202384 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c218485cf0644dbdabea39240518a575
出典データセット
uspto-grants-2016_06
特許番号
US09365545B2

反応ノート

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