Formic Acid → HCID 9818218, compound

HRID 1872672Notes

Reaction equation

HRID 1872672 reaction equation
[CH:1](O)=O.C=O.[Br:6][C:7]1[CH:20]=[C:19]([CH3:21])[C:10]([O:11][CH2:12][C@H:13]2[CH2:18][CH2:17][CH2:16][NH:15][CH2:14]2)=[C:9]([CH3:22])[CH:8]=1>>[Br:6][C:7]1[CH:20]=[C:19]([CH3:21])[C:10]([O:11][CH2:12][C@H:13]2[CH2:18][CH2:17][CH2:16][N:15]([CH3:1])[CH2:14]2)=[C:9]([CH3:22])[CH:8]=1

Participants

4

Reactant 3

HCID 284Formic AcidHCID 712FormaldehydeHCID 15895218HCID 15895218, compound

Product 1

HCID 9818218HCID 9818218, compound

Procedure

Alternatively, formic acid (16.7 mL, 333 mmol) and aqueous formaldehyde (37%, 9.1 mL) were added dropwise to (S)-3-(4-bromo-2,6-dimethylphenoxymethyl)piperidine (24.1 g, 80.8 mmol) that was being chilled in an ice bath. After the addition was complete, the reaction was placed in an oil bath at a temperature of 95° C. for 4 hours. The mixture was cooled to room temperature and partitioned between 15% aqueous sodium hydroxide (200 mL) and ether (600 mL). The aqueous phase was extracted twice more with additional ether (300 mL), and the ether layers combined, washed with brine (150 mL), dried and concentrated. The residue was chromatographed on silica gel, eluting with acetone/hexanes (1:1) and concentrated to give (S)-3-(4-bromo-2,6-dimethylphenoxymethyl)-1-methylpiperidine as a clear oil.

Workup

  1. temperaturewas being chilled in an ice bath
  2. additionAfter the addition
  3. custompartitioned between 15% aqueous sodium hydroxide (200 mL) and ether (600 mL)
  4. extractionThe aqueous phase was extracted twice more with additional ether (300 mL)
  5. washwashed with brine (150 mL)
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel
  9. washeluting with acetone/hexanes (1:1)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-2108011729174136b170a018a389f29e
Source dataset
uspto-grants-2000_08
Patent number
US06110937

Reaction notes

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