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

HRID 1726601Notes

Reaction equation

HRID 1726601 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 intermediate 130, 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-9e25f2d475ce4ecfbc86f5d4aefcff00
Source dataset
uspto-grants-2009_02
Patent number
US07491819B1

Reaction notes

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