tert-Butyl 4-formylpiperidine-1-carboxylate → 4-(2-Furo[3,2-c]pyridin-2-ylvinyl)piperidine-1-carboxylic acid tert-butyl ester

HRID 217181Notes

Reaction equation

HRID 217181 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl.[Br-].[O:13]1[C:21]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[CH:15]=[C:14]1[CH2:22][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][CH:52]([CH:55]=O)[CH2:51][CH2:50]1)=[O:48])([CH3:45])([CH3:44])[CH3:43]>C1COCC1.CCOC(C)=O>[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][CH:52]([CH:55]=[CH:22][C:14]2[O:13][C:21]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]=3[CH:15]=2)[CH2:51][CH2:50]1)=[O:48])([CH3:45])([CH3:43])[CH3:44]

Participants

6

Reactant 3

HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 2733832Lithium HexamethyldisilazideHCID 86629541Furo[3,2-c]pyridin-2-ylmethyltriphenylphosphonium bromide hydrochloride

Product 1

HCID 689404714-(2-Furo[3,2-c]pyridin-2-ylvinyl)piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

LiHMDS (5.9 mL of a 1.0 M solution in THF, 5.90 mmol) was added dropwise to a stirred suspension of furo[3,2-c]pyridin-2-ylmethyltriphenylphosphonium bromide hydrochloride (Preparation 6, 1.50 g, 2.94 mmol) in anhydrous THF (25 mL) at 0° C. After 45 min, the mixture was treated with 4-formylpiperidine-1-carboxylic acid tert-butyl ester (0.63 g, 2.94 mmol), before being stirred at 20° C. for 16 h. The reaction mixture was diluted with EtOAc (300 mL), before being washed with H2O (2×100 mL) and dried (MgSO4). Filtration, solvent evaporation, and flash chromatography (IH-EtOAc, 1:1) furnished 4-(2-furo[3,2-c]pyridin-2-ylvinyl)piperidine-1-carboxylic acid tert-butyl ester: m/z (ES+)=329.1 [M+H]+. This alkene (830 mg, 2.53 mmol) was dissolved in EtOH (15 mL), then Pd (10% on C, 83 mg, 0.08 mmol) was added. The reaction was stirred under a H2 atmosphere for 16 h, before being filtered through celite. The celite was washed with MeOH, then the combined solutions were concentrated to provide the title compound: RT=2.86 min; m/z (ES+)=331.2 [M+H]+.

Workup

  1. washbefore being washed with H2O (2×100 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationFiltration, solvent evaporation, and flash chromatography (IH-EtOAc, 1:1)

Sources & evidence

ORD record
ord-a4f962df0d234a5fa9d8a9ae645ae15c
Source dataset
uspto-grants-2012_06
Patent number
US08193359B2

Reaction notes

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