Hydrochloric Acid → 2-Amino-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanone Hydrochloride

HRID 1685138Notes

Reaction equation

HRID 1685138 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:6]=1)=[O:4].C(OC(=O)C)C.[N:22]12CN3CN(CN(C3)C1)C2.C(O)C.[ClH:35]>>[ClH:35].[NH2:22][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:6]=1)=[O:4]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 4101HexamethylenetetramineHCID 8857Ethyl AcetateHCID 27787872-Bromo-4'-fluoro-3'-(trifluoromethyl)acetophenone

Product 1

HCID 666499872-Amino-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanone HydrochlorideYield 100%

Procedure

To a solution of 2-bromo-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanone (60.00 g 1.00 equiv; 210.50 mmoles (mmol)) in ethylacetate (EA) (450 mL; 4.60 moles (mol)), add 1,3,5,7-tetraazatricyclo-[3.3.1.13,7]decane (Methenamine, 1.10 equiv; 231.55 mmol; 32.46 g) and stir at RT overnight. Remove the solvent in vacuo and triturate the solid with methyl-t-butylether (MTBE), filter and dry in vacuo. Add ethanol (450 mL; 7.73 mol) followed by hydrogen chloride (36.5 wt/wt % in water) (150 mL; 8.30 equiv; 1.75 mol) and stir the mixture overnight. Remove the solvent in vacuo and dry the solid in vacuo at 50° C. for 1 week to give the title compound (54.23 g; 100% yield) as a white solid with some amount of ammonium salt. 1H NMR (300 MHz, DMSO): 8.69-8.59 (m, 4H), 8.07-8.01 (m, 1H), 4.95 (d, J=5.2 Hz, 2H). Use the solid as is.

Workup

  1. customRemove the solvent in vacuo
  2. customtriturate the solid with methyl-t-butylether (MTBE)
  3. filtrationfilter
  4. customdry in vacuo
  5. stirringstir the mixture overnight
  6. customRemove the solvent in vacuo
  7. customdry the solid in vacuo at 50° C. for 1 week

Sources & evidence

ORD record
ord-8556a965119b416a8177e41b2c94a463
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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