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

HRID 541179노트

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HRID 541179 반응식
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]

참가 물질

5

반응물 2

HCID 6228DimethylformamideHCID 183795571-Boc-4-(4-bromo-phenyl)-piperidin-4-ol2회

생성물 1

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

시약·촉매·용매 2

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 178418397HCID 178418397, 화합물촉매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c30a024cd01a4242b2b0cbc439500a99
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871790B2

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