Hydrochloric Acid → Dimethyl-carbamic acid 2-aminomethyl-5-fluoro-phenyl ester hydrochloride

HRID 1372271Notes

Reaction equation

HRID 1372271 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:4]=1[O:10][C:11](=[O:15])[N:12]([CH3:14])[CH3:13])#[N:2].[ClH:16].[H][H]>C(OCC)(=O)C.C(O)C.[Pd]>[ClH:16].[NH2:2][CH2:1][C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:4]=1[O:10][C:11](=[O:15])[N:12]([CH3:13])[CH3:14]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 58777394Dimethyl-carbamic acid 2-cyano-5-fluoro-phenyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 67439203Dimethyl-carbamic acid 2-aminomethyl-5-fluoro-phenyl ester hydrochlorideYield 38%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of intermediate 132, dimethyl-carbamic acid 2-cyano-5-fluoro-phenyl ester, (340 mg, 1.63 mmol) in ethyl acetate (20 mL) and ethanol (20 mL), was added conc.HCl (0.4 mL) and 10% Pd—C (100 mg) and the mixture hydrogenated in a Parr Shaker at 55 psi of hydrogen for 20 hrs. The reaction mixture was filtered through Celite, and the filtrate concentrated in vacuo to give an oil which was partitioned between ethyl acetate (10 mL) and water (10 mL). After separation, the aqueous phase was washed with additional ethyl acetate (5 mL). The combined extracts were concentrated in vacuo to dryness. The residual oil was triturated with ether to provide 145 mg (Yield 38%) of the title compound, as a tan powder: 1H NMR (CD3OD, 500 MHz) δ ppm: 3.06 (3H, s, NMe), 3.21 (3H, s, NMe), 4.11 (2H, s, NCH2), 7.13 (2H, m, Ar—Hs), 7.60 (1H, m, Ar—H); 13C NMR (CD3OD, 125.77 Hz) δ ppm: 36.03, 36.25 37.58, 110.79, 110.99, 113.26, 113.43, 122.32, 132.18, 132.25, 151.55, 154.72, 162.69, 164.67. HRMS (ESI) calcd for C10H13N2O2F (M+H) 213.1039. found 213.1039.

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. concentrationthe filtrate concentrated in vacuo
  3. customto give an oil which
  4. customwas partitioned between ethyl acetate (10 mL) and water (10 mL)
  5. customAfter separation
  6. washthe aqueous phase was washed with additional ethyl acetate (5 mL)
  7. concentrationThe combined extracts were concentrated in vacuo to dryness
  8. customThe residual oil was triturated with ether

Sources & evidence

ORD record
ord-ed8a7f7087184228890ee6f46ad7c83c
Source dataset
uspto-grants-2007_01
Patent number
US07157447B2

Reaction notes

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