Dimethylformamide → Tert-butyl 4-(4-cyanophenyl)-4-hydroxypiperidine-1-carboxylate

HRID 541179ノート

反応式

HRID 541179 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:21])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:22][N:23](C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[C-]#N.[Zn+2]>[C:22]([C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:21])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1)#[N:23]

参加物

5

反応物 2

HCID 6228DimethylformamideHCID 183795571-Boc-4-(4-bromo-phenyl)-piperidin-4-ol2 回

生成物 1

HCID 59003435Tert-butyl 4-(4-cyanophenyl)-4-hydroxypiperidine-1-carboxylate収率 75%

試薬・触媒・溶媒 2

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 178418397HCID 178418397、化合物触媒

実験手順

A solution of tert-butyl 4-(4-bromophenyl)-4-hydroxypiperidine-1-carboxylate (compound 1.1, 36 g, 101.05 mmol, 1.00 equiv), Pd(PPh3)4 (11.7 g, 10.12 mmol, 0.05 equiv), and Zn(CN)2 (17.9 g, 152.44 mmol, 1.51 equiv) in DMF (400 mL) under nitrogen was stirred overnight at 80° C. After reaching ambient temperature, the reaction was then quenched by the addition of 600 mL of FeSO4 (aq., sat.) and diluted with ethyl acetate. The resulting mixture was stirred vigorously then filtered through celite and washed with 1 M FeSO4, water, and ethyl acetate. The layers were separated and the aqueous phase was extracted with 2×300 mL of ethyl acetate. The combined organic layers were washed with 1×200 mL of potassium carbonate (aq., sat.) followed by 1×200 mL of brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:200-1:5) as eluent to yield 23 g (75%) of the title compound as a white solid.

後処理

  1. customAfter reaching ambient temperature
  2. customthe reaction was then quenched by the addition of 600 mL of FeSO4 (aq., sat.)
  3. additiondiluted with ethyl acetate
  4. filtrationthen filtered through celite
  5. washwashed with 1 M FeSO4, water, and ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with 2×300 mL of ethyl acetate
  8. washThe combined organic layers were washed with 1×200 mL of potassium carbonate (aq., sat.)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified

出典と根拠

ORDレコード
ord-c30a024cd01a4242b2b0cbc439500a99
出典データセット
uspto-grants-2014_10
特許番号
US08871790B2

反応ノート

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