Tert-butyl 4-hydroxypiperidine-1-carboxylate → HCID 68709097, compound

HRID 2239372Notes

Reaction equation

HRID 2239372 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][CH:3]=1.[OH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.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]>[C:8]([C:6]1[N:7]=[C:2]([O:10][CH:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH2:16]2)[CH:3]=[CH:4][CH:5]=1)#[N:9]

Participants

6

Reactant 3

HCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 151008596-Bromopyridine-2-carbonitrile

Product 1

HCID 68709097HCID 68709097, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

6-Bromo-2-pyridinecarbonitrile (1.00 g, 5.46 mmol), tert-butyl 4-hydroxypiperidine-1-carboxylate (1.10 g, 5.46 mmol), Pd(OAc)2 (61 mg, 0.27 mmol), 2-(di-t-butylphosphino)biphenyl (98 mg, 0.328 mmol) and Cs2(CO3) (3.56 g, 10.93 mmol) were mixed in toluene (20 ml). The reaction was stirred under an N2 atmosphere and heated to 130° C. on an oil bath for 24 h. The solvent was evaporated in vacuo and the remaining separated between EtOAc (500 ml) and water (500 ml). The aqueous phase was extracted with EtOAc (500 ml). The combined organic phases were washed with water (500 ml), dried with Na2SO4 (s), filtered and evaporated in vacuo. Purification by silica gel flash chromatography using a 40 g Biotage column with a gradient of 5-30% EtOAc in heptane giving the title compound as a white solid. Yield: 605 mg (37%). 1H NMR (400 MHz, CDCl3) δ 7.63 (dd, 1H, J=8.4 Hz, J=7.3 Hz), 7.25 (d, 1H, J=7.3 Hz), 6.90 (d, 1H, J=8.4 Hz), 5.21 (m, 1H), 3.74 (m, 2H), 3.25 (m, 2H), 1.95 (m, 2H), 1.68 (m, 2H), 1.44 (s, 9H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe remaining separated between EtOAc (500 ml) and water (500 ml)
  3. extractionThe aqueous phase was extracted with EtOAc (500 ml)
  4. washThe combined organic phases were washed with water (500 ml)
  5. dry with materialdried with Na2SO4 (s)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customPurification by silica gel flash chromatography

Sources & evidence

ORD record
ord-9f23284c4a174c28a839bebb962047ff
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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