Methanol → 4-Fluoro-2-(2-morpholin-2-yl-2-phenylpropyl)phenol hydrochloride

HRID 899103Notes

Reaction equation

HRID 899103 reaction equation
[CH3:1][S-].[Na+].[ClH:4].[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:27]C)=[C:10]([CH2:12][C:13]([CH:21]2[O:26][CH2:25][CH2:24][NH:23][CH2:22]2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)O)[CH:11]=1.CO>CN(C=O)C>[ClH:4].[F:5][C:6]1[CH:7]=[CH:8][C:9]([OH:27])=[C:10]([CH2:12][C:13]([CH:21]2[O:26][CH2:25][CH2:24][NH:23][CH2:22]2)([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH3:1])[CH:11]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 4378561Sodium methanethiolateHCID 692929272-(5-Fluoro-2-methoxy-phenyl)-1-morpholin-2-yl-1-phenyl-ethanol hydrochloride

Product 1

HCID 692908244-Fluoro-2-(2-morpholin-2-yl-2-phenylpropyl)phenol hydrochlorideYield 69.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium thiomethoxide (13 eq, 186 mg) was added at once to a solution of 2-{2-[5-fluoro-2-(methyloxy)phenyl]-1-methyl-1-phenylethyl}morpholine hydrochloride (75.2 mg, 0.204 mmol, synthesized as described in Example 8 above) in anydrous DMF (3 ml) in a microwave vessel. Upon addition, the reaction vessel was sealed and heated up in a CEM-Discovery microwave at 150 Watts, reaching 110° C. in 5 minutes and maintaining this temperature 6 minutes. The reaction vessel was cooled to room temperature and the reaction mixture taken into methanol (5 ml) and purified by SCX-2 chromatography to obtain the free base as clear oil (50 mg). The hydrochloride salt was obtained following general procedures as a white solid (52 mg, 72% after salt formation.). MW 353.83; C18H22NO3FCl; 1H NMR (CD3OD): 7.29-7.26 (2H, m), 7.20-7.08 (2H, m), 6.53-6.50 (2H, m), 6.30-6.26 (1H, m), 4.18 (1H, dd, 12.6 Hz, 2.6 Hz), 4.02 (1H, dd, 10.9 Hz, 2.3 Hz), 3.86 (1H, td, 12.6 Hz, 2.6 Hz), 3.60 (1H, 1/2 AB), 3.16 (1H, d, 12.6 Hz), 3.08-2.90 (3H, m), 2.58 (1H, m); 19F NMR (CD3OD)-128.4; LCMS: (12 min method) m/z 318.1 [M−HCl+H]+ @ Rt 3.954 min.

Workup

  1. additionUpon addition
  2. customthe reaction vessel was sealed
  3. temperatureheated up in a CEM-Discovery microwave at 150 Watts
  4. temperaturemaintaining this temperature 6 minutes
  5. custompurified by SCX-2 chromatography

Sources & evidence

ORD record
ord-a157f0043ed5410bb633d7745a44ecb5
Source dataset
uspto-grants-2008_04
Patent number
US07354920B2

Reaction notes

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