Acetic Acid → HCID 57893614, compound

HRID 1822030Notes

Reaction equation

HRID 1822030 reaction equation
[Cl:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH:14]2[CH2:19][CH2:18][NH:17][CH:16]([CH3:20])[CH2:15]2)[CH:8]=1)=[O:5].C=O.[C:28](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C@H:14]2[CH2:19][CH2:18][N:17]([CH3:28])[C@@H:16]([CH3:20])[CH2:15]2)[CH:8]=1)=[O:5]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 69069089HCID 69069089, compound

Product 1

HCID 57893614HCID 57893614, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Combine 2-chloro-4-fluoro-N-[3-(2-methyl-piperidin-4-yloxy)-phenyl]-benzamide cis isomer 1 (example 57, 0.26 g, 0.72 mmol), dichloromethane (20 mL), and 37% aqueous formaldehyde (0.58 mL, 7.2 mmol) with stirring. After 10 min., add glacial acetic acid (0.08 mL, 1.44 mmol) followed by sodium triacetoxyborohydride (0.23 g, 1.08 mmol). After 3 hr., partition between 1M aqueous sodium hydroxide solution (50 mL) and dichloromethane (50 mL). Separate the organic layer, wash with aqueous NaCl solution, dry over sodium sulfate, filter and concentrate. Purify residue by silica gel flash chromatography eluting with 10% (2M ammonia/methanol) in dichloromethane to obtain of the title compound (0.46 g, 85%). Mass spectrum: Obs. m/z 377.1443; Calc. m/z 377.1432; mp: 152° C.

Workup

  1. waitAfter 3 hr
  2. custom, partition between 1M aqueous sodium hydroxide solution (50 mL) and dichloromethane (50 mL)
  3. customSeparate the organic layer
  4. washwash with aqueous NaCl solution
  5. dry with materialdry over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. washPurify residue by silica gel flash chromatography eluting with 10% (2M ammonia/methanol) in dichloromethane

Sources & evidence

ORD record
ord-08897fc038e34ab3a14dd4a1e6761958
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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