Hydrochloric Acid → 2-(2-(Aminomethyl)-5-fluorophenoxy)-1-morpholinoethanone hydrochloride

HRID 1664168Notes

Reaction equation

HRID 1664168 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])[CH:3]=1.[ClH:20].[H][H]>C(O)C.C(OCC)(=O)C.[Pd]>[ClH:20].[NH2:7][CH2:6][C:5]1[CH:8]=[CH:9][C:2]([F:1])=[CH:3][C:4]=1[O:10][CH2:11][C:12]([N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)=[O:13]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 210698914-Fluoro-2-(2-morpholino-2-oxoethoxy)benzonitrileHCID 178418361HCID 178418361, compound

Product 1

HCID 210697802-(2-(Aminomethyl)-5-fluorophenoxy)-1-morpholinoethanone hydrochlorideYield 29.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalyst2×HCID 702EthanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-fluoro-2-(2-morpholino-2-oxoethoxy)benzonitrile, (500 mg, 1.89 mmol) in warm ethanol (30 mL) and ethyl acetate (30 mL) was mixed with conc.HCl (0.32 mL, 3.78 mmol, 2 eq.). To this was added 10% Pd—C (100 mg; Aldrich), and the mixture was hydrogenated at 1 atm of hydrogen for 20 hrs at room temperature. To this mixture was added an additional amount of 10% Pd—C (50 mg) and stirring continued for another 7 hrs. The mixture was filtered through Celite® and the filtrate concentrated in vacuo to dryness. The residue was triturated with ethyl acetate, then with ethanol to obtain the title compound (168 mg, Yield 29%) as an off-white powder: 1H NMR (CD3OD, 500 MHz) δ ppm: 3.55 (2H, t, J=5 Hz, NCH2), 3.62 (2H, t, J=5 Hz, NCH2), 3.70 (2H, t, J=5 Hz, OCH2), 3.75 (2H, t, J=5 Hz, OCH2), 4.17 (2H, s, NCH2), 5.17 (2H, s, OCH2), 6.82 (1H, dt, J=2.5, 8.5 Hz, Ar—H), 7.05 (1H, dd, J=2.5, 10.5 Hz, Ar—H), 7.43 (1H, dd, J=6.5, 8.5 Hz, Ar—H); 13C NMR (CD3OD, 125.77 Hz) δ ppm: 39.40, 42.49, 44.97, 66.11, 66.46, 66.59, 101.38, 101.59, 108.40, 108.57, 118.40, 132.53, 132.62, 158.43, 158.52, 63.87, 165.83, 168.27. HRMS (ESI) calcd for C13H18N2O3F (M+H) 269.1301, found 269.1301.

Workup

  1. filtrationThe mixture was filtered through Celite®
  2. concentrationthe filtrate concentrated in vacuo to dryness
  3. customThe residue was triturated with ethyl acetate

Sources & evidence

ORD record
ord-840b21bf2b234085b68fa1d633b7711e
Source dataset
uspto-grants-2011_10
Patent number
US08039458B2

Reaction notes

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