Water → HCID 68468177, compound

HRID 736367Notes

Reaction equation

HRID 736367 reaction equation
O[CH:2]1[CH:7]([CH2:8][CH2:9][O:10][CH:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6][CH2:5][N:4]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[CH2:3]1.C(N(CC)CC)C.[C:39](Cl)(=[O:42])[CH2:40][CH3:41].O>C(Cl)Cl>[C:39]([C@H:2]1[C@H:7]([CH2:8][CH2:9][O:10][CH:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:6][CH2:5][N:4]([CH2:24][C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[CH2:3]1)(=[O:42])[CH2:40][CH3:41]

Participants

6

Reactant 4

HCID 962WaterHCID 8471Triethylamine2×HCID 62324Propionyl chloride2×HCID 10223844HCID 10223844, compound

Product 1

HCID 68468177HCID 68468177, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 61 mg 3-hydroxy-4-[2-(diphenylmethoxy)ethyl]-1-[(4-fluorophenyl)methyl]piperidine (0.15 mmol) and 21 mg triethylamine (0.23 mmol, 1.5 equiv) in 2 mL CH2Cl2 cooled in an ice bath was added dropwise 18 mg propionyl chloride (0.19 mmol, 1.3 equiv) and the reaction was allowed to warm to RT. After 1 hr, the same quantities of triethylamine and propionyl chloride were added. After 1 hr, H2O was added and the organic layer was separated, dried (MgSO4) and evaporated. The remaining residue was chromatographed (SiO2; CH2Cl2/MeOH) to yield the title compound as the free base (53 mg, 77%). 1H NMR (CdCl3 ∂ 1.1 (3H, t, J=8.1 Hz), 1.26-1.95 (7H, m), 2.26 (2H, q, J=7.2 and 7.5 Hz), 2.71 (1H, d, J=11.7 Hz), 3.02 (1H, d, J=10.5 Hz), 3.41-3.52 (4H, m), 4.67 (1H, t, J=9.6 Hz), 5.31 (1H, s), 6.98 (2H, t, J=9.3 Hz), 7.2-7.4 (12H, m). This was then reacted in a mixture of 2 mL 50% EtOH/Et2O with oxalic acid dihydrate (15.4 mg, 1.1 equiv) to furnish the title compound. mp ° C. Elemental analysis calculated for C32H36NO7F·0.5 H2O: C, 67.43; H, 6.41; N, 2.46. Found: C, 67.34; H, 6.43; N, 2.44.

Workup

  1. waitAfter 1 hr
  2. customthe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe remaining residue was chromatographed (SiO2; CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-53623e554e274d27b3d3f8394e3c1b9a
Source dataset
uspto-grants-2009_09
Patent number
US07595331B2

Reaction notes

Loading…