tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-hydroxypiperidine-1-carboxylate

HRID 514847ノート

反応式

HRID 514847 の反応式
[C:1]([Si:5]([CH3:11])([CH3:10])[O:6][CH2:7][C:8]#[CH:9])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[O:17]=[C:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1>C1COCC1>[Si:5]([O:6][CH2:7][C:8]#[C:9][C:18]1([OH:17])[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:22][CH2:23]1)([C:1]([CH3:3])([CH3:4])[CH3:2])([CH3:10])[CH3:11]

参加物

5

反応物 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 3445622Propargyloxy-t-butyldimethylsilaneHCID 178418339Butyllithium

生成物 1

HCID 90418995Tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-hydroxypiperidine-1-carboxylate収率 121%

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-butyldimethyl(prop-2-yn-1-yloxy)silane (0.5 mL, 2.46 mmol) in 30 mL of anhydrous THF was added dropwise n-BuLi (1.2 mL, 2.95 mmol) at −78° C. under N2. After stirring for 1 h at −78° C., tert-butyl 4-oxopiperidine-1-carboxylate (588.4 mg, 2.95 mmol) in THF (2 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 1.5 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 to afford 1.10 g of title compound. LC-MS: m/z 370.7 (M+H)+. 1H NMR (CHLOROFORM-d) δ: 4.37 (s, 2H), 3.74 (d, J=6.2 Hz, 2H), 3.35-3.24 (m, 2H), 2.46 (t, J=6.2 Hz, 1H), 1.92-1.84 (m, 2H), 1.71 (ddd, J=12.9, 9.1, 3.8 Hz, 2H), 1.47 (s, 9H), 0.92 (s, 9H), 0.13 (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 1.5 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-7c545f8c100e4796b48eb77d921ebde2
出典データセット
uspto-grants-2015_08
特許番号
US09108921B2

反応ノート

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