Hydrochloric Acid → 3,5-Difluoro-4-methoxy-α-methylbenzenemethanamine

HRID 911318Notes

Reaction equation

HRID 911318 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:11](=O)[CH3:12])[CH:5]=[C:6]([F:10])[C:7]=1[O:8][CH3:9].C([O-])(=O)C.[NH4+].C([BH3-])#[N:20].[Na+].Cl>CO>[F:1][C:2]1[CH:3]=[C:4]([CH:11]([NH2:20])[CH3:12])[CH:5]=[C:6]([F:10])[C:7]=1[O:8][CH3:9]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 517165Ammonium AcetateHCID 27369833',5'-Difluoro-4'-methoxyacetophenoneHCID 5003444Sodium cyanoborohydride

Product 1

HCID 552735193,5-Difluoro-4-methoxy-α-methylbenzenemethanamineYield 40.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Slurry 3′,5′-difluoro-4′-methoxyacetophenone (1.0 g, 5.0 mmol), ammonium acetate (4.14 g, 50 mmol) and sodium cyanoborohydride (630 mg, 20 mmol) in anhydrous methanol (35 mL) and stir for 18 h at ambient temperature. Acidify with 1N aqueous HCl (5 mL), dilute, extract with ethyl ether (3×150 mL), basify aqueous with 1N aqueous NaOH, extract with DCM (3×50 mL), wash the organic extracts with brine, dry over MgSO4, filter and concentrate in vacuo. Purify by SCX chromatography to give crude the title compound as a yellow oil (380 mg).

Workup

  1. additiondilute
  2. extractionextract with ethyl ether (3×150 mL), basify aqueous with 1N aqueous NaOH
  3. extractionextract with DCM (3×50 mL)
  4. washwash the organic extracts with brine
  5. dry with materialdry over MgSO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify by SCX chromatography

Sources & evidence

ORD record
ord-4202df28a1e44c32977ebc6ea71649df
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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