Boron trifluoride etherate → HCID 59382917, compound

HRID 1254394Notes

Reaction equation

HRID 1254394 reaction equation
B(F)(F)F.CCOCC.[H-].[Na+].[Cl:12][C:13]1[CH:14]=[C:15]([C:19]2([C@@H:22]3[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23]3)[CH2:21][O:20]2)[CH:16]=[CH:17][CH:18]=1.[CH3:35][O:36][CH2:37][CH2:38][OH:39]>>[Cl:12][C:13]1[CH:14]=[C:15]([C@:19]([C@@H:22]2[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:33])([CH3:34])[CH3:32])=[O:29])[CH2:23]2)([OH:20])[CH2:21][O:39][CH2:38][CH2:37][O:36][CH3:35])[CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 4

HCID 8000Boron trifluoride etherateHCID 80192-MethoxyethanolHCID 24758Sodium hydrideHCID 59383070HCID 59383070, compound

Product 1

HCID 59382917HCID 59382917, compound

Procedure

A stirred solution of BF3.Et2O (12.9 mg, 0.0592 mmol) and NaH (22.6 mg, 0.296 mmol) in 2-methoxyethanol (10 mL) was warmed to 55-60° C. and (3R)-tert-butyl 3-(2-(3-chlorophenyl)oxiran-2-yl)piperidine-1-carboxylate (100 mg, 0.296 mmol) was added dropwise. After addition, the reaction mixture was stirred at the same temperature overnight. The reaction mixture was concentrated and the residue was partitioned between H2O and EtOAc. The organic layer washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. LC-MS analysis of the crude product indicated the presence of two isomers. The crude product was purified by preparative HPLC to give the major isomer (R)-tert-butyl 3-((S)-1-(3-chlorophenyl)-1-hydroxy-2-(2-methoxyethoxy)ethyl)piperidine-1-carboxylate (30 mg, 0.073 mmol); 1H NMR (400 MHz, CDCl3): 1.33 (s, 9H), 1.65 (m, 1H), 1.74 (m, 1H), 1.96 (m, 1H), 2.47 (m, 2H), 3.26 (m, 2H), 3.33 (s, 3H), 3.46 (m, 2H), 3.61 (m, 2H), 3.79 (m, 1H), 3.84 (m, 1H), 3.99 (m, 1H), (m, 1H), 7.22 (m, 3H), 7.42 (s, 1H); MS (E/Z): 414 (M+H+)

Workup

  1. additionAfter addition
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was partitioned between H2O and EtOAc
  4. washThe organic layer washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-9fca0bca880a45d49316c13264c9dd2c
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

Loading…