Water → Tert-butyl 4-(3-hydroxybenzylidene)piperidine-1-carboxylate

HRID 1666432Notes

Reaction equation

HRID 1666432 reaction equation
Br[CH:2]=[C:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[OH:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>C1COCC1>[OH:16][C:17]1[CH:22]=[C:21]([CH:20]=[CH:19][CH:18]=1)[CH:2]=[C:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 45489892tert-Butyl 4-(bromomethylidene)piperidine-1-carboxylate

Product 1

HCID 53485958Tert-butyl 4-(3-hydroxybenzylidene)piperidine-1-carboxylateYield 66.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of tert-butyl 4-(bromomethylene)piperidine-1-carboxylate (38 g, 0.1376 mol) in dry THF (380 mL) was added 3-hydroxyphenyl boronic acid (22.77 g, 0.165 mol), potassium phosphate (88.2 g, 0.415 mol) and water (7.6 mL). The mixture was degassed with argon. 1,1′-Bis(diphenylphosphino)ferrocene palladium(II) dichloride dichloromethane complex (11.23 g, 0.01376 mol) was added and the mixture was degassed again. The reaction was heated at 50° C. for 1.5 h and then allowed to cool to RT. Water was added and the mixture was extracted with ethyl acetate (3×). The total organic extract was washed with brine, dried over sodium sulfate and evaporated to dryness. The residue was purified by silica gel chromatography using 100-200 mesh silica gel (8% ethyl acetate in hexane) to give the title compound (26.3 g, 66%). 1H NMR (500 MHz, CDCl3): δ 7.16 (t, J=7.5 Hz, 1H), 6.74 (d, J=7.5 Hz, 1H), 6.68 (d, J=9 Hz, 1H), 6.68 (s, 1H), 6.30 (s, 1H), 5.37 (bs, 1H), 3.49 (m, 2H), 3.40 (m, 2H), 2.46 (m, 2H), 2.31 (m, 2H), 1.48 (s, 9H); 13C NMR (125 MHz, CDCl3): δ 156.09, 155.09, 138.87, 138.15, 129.31, 124.58, 120.98, 115.74, 113.54, 80.10, 45.45, 44.57, 36.08, 29.23, 28.50.

Workup

  1. customThe mixture was degassed with argon
  2. addition1,1′-Bis(diphenylphosphino)ferrocene palladium(II) dichloride dichloromethane complex (11.23 g, 0.01376 mol) was added
  3. customthe mixture was degassed again
  4. temperatureto cool to RT
  5. additionWater was added
  6. extractionthe mixture was extracted with ethyl acetate (3×)
  7. extractionThe total organic extract
  8. washwas washed with brine
  9. dry with materialdried over sodium sulfate
  10. customevaporated to dryness
  11. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-6490091ed6844c658cfb6e25e90b551b
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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