Hydrochloric Acid → Lofexidine Hydrochloride

HRID 423436Notes

Reaction equation

HRID 423436 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[C:3]=1[O:4][CH:5]([C:7]1[NH:8][CH2:9][CH2:10][N:11]=1)[CH3:6].CCOCC.CC(O)C.Cl>CCOCC>[ClH:1].[Cl:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[C:3]=1[O:4][CH:5]([C:7]1[NH:11][CH2:10][CH2:9][N:8]=1)[CH3:6]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 30668LofexidineHCID 22147583Diethyl ether 2-propanol

Product 1

HCID 30667Lofexidine HydrochlorideYield 197.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of 3 (10.00 g, 39 mmol) in 4:1 ether/i-PrOH (100 mL) was added dropwise conc. aqueous HCl (3.5 mL, 1.1 equiv.). Upon stirring for 10 minutes the suspension was diluted with ether (100 mL), filtered and the filter-cake was washed with ether (3×50 mL) and air-dried, affording 26 (11.40 g, 100%). 1H NMR (300 MHz, d6-DMSO) δ ppm 10.86 (s, 2H, NH), 7.52 (d, J=8.1 Hz, 2H, Ar), 7.23 (t, J=8.1 Hz, 1H, Ar), 5.20 (q, J=6.6 Hz, 1H) 3.87 (s, br, 4H), 1.66 (d, J=6.6 Hz, 3H); 13C NMR (75 MHz, d6-DMSO) δ ppm 169.5, 149.2, 130.3, 129.1, 127.5, 73.9, 45.2, 19.5; mp=226-227° C.; [α]23D=−39.0° (c 1.0, EtOH) (lit.5 [α]20D −34.5° (c 1.0, EtOH).

Workup

  1. filtrationfiltered
  2. washthe filter-cake was washed with ether (3×50 mL)
  3. customair-dried

Sources & evidence

ORD record
ord-f85d9287ccb94a80a3f5f0a5d4d3a7ef
Source dataset
uspto-grants-2012_01
Patent number
US08101779B2

Reaction notes

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