Methylamine → 4-fluoro-N-methylbenzamide

HRID 2361635Notes

Reaction equation

HRID 2361635 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][CH:3]=1.CN.C1COCC1.C[CH2:19][N:20](CC)CC.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>ClCCCl>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:20][CH3:19])=[O:7])=[CH:4][CH:3]=1

Participants

8

Reactant 6

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 99734-Fluorobenzoic AcidHCID 10868DicyclohexylcarbodiimideHCID 757711-Hydroxybenzotriazole

Product 1

HCID 40742474-fluoro-N-methylbenzamideYield 63%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 4-fluorobenzoic acid (200 mg, 1.43 mmol) in DCE (3 ml) at RT, was added a solution of methyl amine in THF (2 M, 1.43 mmol) and NEt3 (198 μl, 1.43 mmol) and allowed to stir for ca. 10 mins. HOBt (221 mg, 1.43 mmol) and DCC (295 mg, 1.43 mmol) were added and the reaction mixture heated at 70° C. for 3 h. After cooling to RT, the reaction mixture was washed with sat. NaHCO3 (5 ml) and the aqueous back extracted with DCM. The organics were combined, dried (MgSO4), filtered and concentrated under reduced pressure. Purification by silica flash column chromatography (eluting with DCM/MeOH gradient 100:0 to 80:20) provided the title compound as off-white solid (137 mg, 63%).

Workup

  1. temperatureAfter cooling to RT
  2. washthe reaction mixture was washed with sat. NaHCO3 (5 ml)
  3. extractionthe aqueous back extracted with DCM
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification
  8. washby silica flash column chromatography (eluting with DCM/MeOH gradient 100:0 to 80:20)

Sources & evidence

ORD record
ord-b0056f459b7447a593e832cfa24f4b1c
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

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