Cesium carbonate → tert-Butyl 4-{[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridin-2-yl]oxy}piperidine-1-carboxylate

HRID 2239360Notes

Reaction equation

HRID 2239360 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[N:3]=1.[OH:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[Si:10]([O:9][CH2:8][C:4]1[N:3]=[C:2]([O:17][CH:18]2[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:22][CH2:23]2)[CH:7]=[CH:6][CH:5]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 11483477Pyridine, 2-bromo-6-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-

Product 1

HCID 68709259tert-Butyl 4-{[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridin-2-yl]oxy}piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

2-Bromo-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridine (2.7 g, 7.51 mmol), tert-butyl 4-hydroxypiperidine-1-carboxylate (1.5 g, 7.51 mmol), palladium(II) acetate (0.034 g, 0.15 mmol), biphenyl-2-yl(di-tert-butyl)phosphine (0.056 g, 0.19 mmol) and cesium carbonate (4.9 g, 15.0 mmol) were mixed in a 40 mL vial and dry toluene (25 ml) was added. The vial was then briefly evacuated and backfilled with N2 five times, and the reaction vessel was heated at 100° C. under N2 atmosphere for 24 hours. The reaction mixture was cooled to room temperature. The reaction mixture was diluted with toluene (100 mL), washed with water, the organics dried over MgSO4 and concentrated in vacuo. Purification by flash chromatography using a gradient with toluene:EtOAc (98:2-80:20), gave the product as an oil. Yield: 1.1 g (33%). 1H NMR (400 MHz, CDCl3) δ 7.44 (t, 1H, J=7.82 Hz), 6.89 (d, 1H, J=7.30 Hz), 6.43 (d, 1H, J=8.34 Hz), 5.04-5.11 (m, 1H), 4.56 (s, 2H), 3.58-3.68 (m, 2H), 3.12-3.21 (m, 2H), 1.78-1.87 (m, 2H), 1.53-1.64 (m, 2H), 1.35 (s, 9H), 0.84 (s, 9H), 0.00 (s, 6H). MS (ESI+) 423.24 (M+1H+).

Workup

  1. customThe vial was then briefly evacuated
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionThe reaction mixture was diluted with toluene (100 mL)
  4. washwashed with water
  5. dry with materialthe organics dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-fcc09f1b491f4d3fb85cf2cf03d219d0
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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