Acetic Acid → HCID 67751248, compound

HRID 2210691Notes

Reaction equation

HRID 2210691 reaction equation
Cl.[CH3:2][C:3]1[CH:4]=[C:5]([CH2:10][O:11][C@H:12]2[CH2:17][CH2:16][CH2:15][NH:14][C@H:13]2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=[C:7]([CH3:9])[CH:8]=1.[C:24](O)(=O)C.C([BH3-])#N.[Na+].C=O>CO>[CH3:9][C:7]1[CH:6]=[C:5]([CH2:10][O:11][C@H:12]2[CH2:17][CH2:16][CH2:15][N:14]([CH3:24])[C@H:13]2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:4]=[C:3]([CH3:2])[CH:8]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 67751568HCID 67751568, compound

Product 1

HCID 67751248HCID 67751248, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

A solution of cis-3-((3,5-dimethylphenyl)methyloxy)-2-phenylpiperidine (220 mg, 0.75 mmol, Example 2) and acetic acid (0.212 ml) in dry methanol (6 ml) was cooled to 0° C. and sodium cyanoborohydride (96 mg, 1.5 mmol) was added followed by formaldehyde (38% aq. solution, 0.15 ml). The reaction mixture was stirred at 23° C. for 18 h, then the solvent was removed in-vacuo and the residue partitioned between dichloromethane and 2M sodium hydroxide. The layers were separated, and the aqueous phase extracted with dichloromethane (2×20 ml). The combined organic extracts were washed with water then brine, then dried (K2CO3) and concentrated to leave a clear oil. Purification on silica-gel (CH2Cl2 /MeOH/NH3 97:3:0.5 then CH2Cl2 /MeOH 90:10) provided the title compound as a clear, colourless oil. 1H NMR (CDCl3) 7.42 (m), 7.30 (m), 6.77 (s), 6.54 (s), 4.27 (d, J=12.2 Hz), 4.04 (d, J=12.2 Hz), 3.42 (s), 3.07 (m), 2.91 (d, J=1.9 Hz), 2.17 (s), 2.10 (m) 2.04 (s), 1.56 (m), 1.39 (m). MS (CI) m/z 310 (MH).

Workup

  1. customthe solvent was removed in-vacuo
  2. customthe residue partitioned between dichloromethane and 2M sodium hydroxide
  3. customThe layers were separated
  4. extractionthe aqueous phase extracted with dichloromethane (2×20 ml)
  5. washThe combined organic extracts were washed with water
  6. dry with materialbrine, then dried (K2CO3)
  7. concentrationconcentrated
  8. customto leave a clear oil
  9. customPurification on silica-gel (CH2Cl2 /MeOH/NH3 97:3:0.5

Sources & evidence

ORD record
ord-8c7bb77a0c5c4880bd8f63c5664ca341
Source dataset
uspto-grants-1995_10
Patent number
US05459270

Reaction notes

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