2-(Di-tert-butylphosphino)biphenyl → HCID 86618692, compound

HRID 2239366Notes

Reaction equation

HRID 2239366 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][CH2:18][C@@H:19]1[CH2:24][CH2:23][CH2:22][CH2:21][N:20]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Si:10]([O:9][CH2:8][C:4]1[N:3]=[C:2]([O:17][CH2:18][C@@H:19]2[CH2:24][CH2:23][CH2:22][CH2:21][N:20]2[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:7]=[CH:6][CH:5]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

6

Reactant 3

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 6933954tert-Butyl (2S)-2-(hydroxymethyl)piperidine-1-carboxylateHCID 11483477Pyridine, 2-bromo-6-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-

Product 1

HCID 86618692HCID 86618692, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

2-Bromo-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridine (702 mg, 2.32 mmol, from Example 21a), tert-butyl (2S)-2-(hydroxymethyl)piperidine-1-carboxylate (500 mg, 2.32 mmol), Pd(OAc)2 (26 mg, 0.116 mmol), 2-(di-t-butylphosphino)biphenyl (42 mg, 0.139 mmol) and Cs2(CO3) (1.51 g, 4.64 mmol) were mixed in toluene (20 ml). The reaction was stirred under an N2 atmosphere and heated to 100° C. on an oil bath for 24 h. The solvent was evaporated in vacuo and the residue separated between EtOAc (250 ml) and water (250 ml). The organic phase washed with water (250 ml) and the combined aqueous phases were extracted with EtOAc (250 ml). The combined EtOAc phases were dried over Na2SO4 (s), filtered and evaporated in vacuo. Purification by silica gel flash chromatography using a 40+M Biotage column with a gradient of 5-20% EtOAc in heptane yielded the title compound as a colorless oil. Yield: 729 mg (72%). 1H NMR (400 MHz, CDCl3) δ 7.43 (t, 1H, J=7.8 Hz), 6.91 (d, 1H, J=7.3 Hz), 6.44 (d, 1H, J=8.2 Hz), 4.57 (s, 2H), 4.48 (m, 1H), 4.25 (d, 2H, J=7.4 Hz), 3.91 (d, 1H, J=11.6 Hz), 2.76 (dt, 1H, J=13.3 Hz, J=2.0 Hz), 1.69 (d, 1H, J=12.0 Hz), 1.57-1.37 (m, 5H), 1.27 (s, 9H), 0.84 (s, 9H), 0.00 (s, 6H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue separated between EtOAc (250 ml) and water (250 ml)
  3. washThe organic phase washed with water (250 ml)
  4. extractionthe combined aqueous phases were extracted with EtOAc (250 ml)
  5. dry with materialThe combined EtOAc phases were dried over Na2SO4 (s)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customPurification by silica gel flash chromatography

Sources & evidence

ORD record
ord-7af6daadb4a7450796743dbaa0b865ed
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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