Methanol → HCID 86596808, compound

HRID 1788279Notes

Reaction equation

HRID 1788279 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:16]2[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][CH:17]=2)([C:14]#N)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.[CH3:32][OH:33]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:16]2[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][CH:17]=2)([CH2:14][CH:32]=[O:33])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 14487Diisobutylaluminum hydrideHCID 49760269Tert-butyl 4-(4-bromophenyl)-4-cyanopiperidine-1-carboxylate

Product 1

HCID 86596808HCID 86596808, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(4-bromo-phenyl)-4-cyano-piperidine-1-carboxylic acid tert-butyl ester from Step 2 (5.67 g, 15.57 mmol, 1 eq) in 60 mL of dichloromethane was add a solution of DIBAL-H (1M in toluene, 23.36 mL, 23.36 mmol, 1.5 eq) in a drop-wise fashion. The resulting mixture was stirred at room temperature for 20 h and then 15 mL of methanol was added carefully. The mixture was stirred for 0.25 h and a precipitate formed. The resulting mixture was filtered through Celite and the salts were washed several times with ethyl acetate. The filtrate was adsorbed onto silica gel and purified by flash column chromatography eluting with a gradient of 5-20% ethyl acetate in hexane to give 1.78 g of 4-(4-bromo-phenyl)-4-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl ester and 1.54 g of recovered starting material. 1H NMR (300 MHz, CDCl3): δ 9.35 (s, 1H), 7.50-7.46 (d, 2H), 7.15-7.10 (d, 2H), 3.82 (br. s, 2H), 3.11-3.04 (t, 2H), 2.35-2.28 (dt, 2H), 1.90 (br. s, 2H), 1.42 (s, 9H).

Workup

  1. stirringThe mixture was stirred for 0.25 h
  2. customa precipitate formed
  3. filtrationThe resulting mixture was filtered through Celite
  4. washthe salts were washed several times with ethyl acetate
  5. custompurified by flash column chromatography
  6. washeluting with a gradient of 5-20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-26a28e9c09a047ae98dac8af6f50f05b
Source dataset
uspto-grants-2009_03
Patent number
US07511146B2

Reaction notes

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