Water → 1-(1-Benzylpiperidin-4-yl)-2-formyl-4-phenylbutan-1-one

HRID 1862651Notes

Reaction equation

HRID 1862651 reaction equation
C[C:2](C)([O-:4])C.[K+].[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([C:20](=[O:30])[CH2:21][CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(OC)=O.O>C1COCC1>[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([C:20](=[O:30])[CH:21]([CH:2]=[O:4])[CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:16][CH2:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7865Methyl formateHCID 181875541-(1-Benzylpiperidin-4-yl)-4-phenylbutan-1-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 181877591-(1-Benzylpiperidin-4-yl)-2-formyl-4-phenylbutan-1-oneYield 103.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of potassium t-butoxide (0.673 g) in THF (20 mL) under nitrogen and cooled in an ice bath was added a solution of 1-(1-benzylpiperidin-4-yl)-4-phenylbutan-1-one from Step D (0.71 g) and methyl formate (3.76 mL) in THF (12 mL) over 5 minute. The reaction was stirred for 15 min before being allowed to warm to rt for 2 h. The reaction was poured into water and extracted with ether (4×100 mL), methylene chloride (100 mL), and THF (100 mL). The combined organic layers were washed with water and brine, dried over sodium sulfate and concentrate under reduced pressure. The crude product was purified by FC on silica gel eluting with 5 and 20% methanol in ethyl acetate with 4% TEA to afford the title compound (0.8 g).

Workup

  1. extractionextracted with ether (4×100 mL), methylene chloride (100 mL), and THF (100 mL)
  2. washThe combined organic layers were washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrate under reduced pressure
  5. customThe crude product was purified by FC on silica gel eluting with 5 and 20% methanol in ethyl acetate with 4% TEA

Sources & evidence

ORD record
ord-3a11aeab1801448da1b8db2edf560d8c
Source dataset
uspto-grants-2003_03
Patent number
US06538002B1

Reaction notes

Loading…