Water → tert-butyl N-[(3S)-1-[6-bromo-3-(hydroxymethyl)-2-pyridyl]-3-piperidyl]carbamate

HRID 57918Notes

Reaction equation

HRID 57918 reaction equation
[Br:1][C:2]1[N:7]=[C:6](F)[C:5]([CH2:9][OH:10])=[CH:4][CH:3]=1.[NH:11]1[CH2:16][CH2:15][CH2:14][C@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:12]1.CN1CCOCC1.O>CN1CCCC1=O>[Br:1][C:2]1[N:7]=[C:6]([N:11]2[CH2:16][CH2:15][CH2:14][C@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH2:12]2)[C:5]([CH2:9][OH:10])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 79724-MethylmorpholineHCID 1514171tert-butyl N-[(3S)-piperidin-3-yl]carbamateHCID 71303921(6-Bromo-2-fluoropyridin-3-YL)methanol

Product 1

HCID 86707108tert-butyl N-[(3S)-1-[6-bromo-3-(hydroxymethyl)-2-pyridyl]-3-piperidyl]carbamateYield 80.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of (6-bromo-2-fluoro-3-pyridyl)methanol (1.766 mmol; 363.8 mg), tert-butyl N-[(3S)-3-piperidyl]carbamate (2.649 mmol; 530.5 mg), and N-Methylmorpholine (5.298 mmol; 541 mg; 0.588 mL) in 1-methyl-2-pyrrolidinone (10 mL) in a sealed pressure vial was heated at 130° C. for 4 hours. The mixture was poured into water, and extracted with EtOAc. The organic layer was concentrated. The residue was purified on silica eluted with 0 to 100% EtOAc in Heptane to afford tert-butyl N-[(3S)-1-[6-bromo-3-(hydroxymethyl)-2-pyridyl]-3-piperidyl]carbamate (546.3 mg, 80%).

Workup

  1. extractionextracted with EtOAc
  2. concentrationThe organic layer was concentrated
  3. customThe residue was purified on silica
  4. washeluted with 0 to 100% EtOAc in Heptane

Sources & evidence

ORD record
ord-9cea2d1bb0e74d9faf37d26e2b47a6ea
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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