Ammonium Chloride → (1S,2S)-2-Amino-3-(3-isopropylsulfanyl-5-fluorophenyl)-1-[(3R,5S,6R)-6-(2,2-di-(fluoromethyl)propoxy)-5-methylmorpholin-3-yl]-propan-1-ol

HRID 20456Notes

Reaction equation

HRID 20456 reaction equation
[NH2:1][C@@H:2]([CH2:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[C:23](F)[CH:22]=1)[C@@H:3]([C@H:5]1[CH2:10][O:9][C@@H:8]([O:11][CH2:12][C:13]([CH2:17][F:18])([CH2:15][F:16])[CH3:14])[C@H:7]([CH3:19])[NH:6]1)[OH:4].[CH3:29][CH:30]([S-:32])[CH3:31].[Na+].[Cl-].[NH4+]>CN1CCCC1=O.CO>[NH2:1][C@@H:2]([CH2:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([S:32][CH:30]([CH3:31])[CH3:29])[CH:22]=1)[C@@H:3]([C@H:5]1[CH2:10][O:9][C@@H:8]([O:11][CH2:12][C:13]([CH2:17][F:18])([CH2:15][F:16])[CH3:14])[C@H:7]([CH3:19])[NH:6]1)[OH:4]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 3470666Sodium 2-propanethiolateHCID 68560607(1S,2S)-2-Amino-3-(3,5-difluorophenyl)-1-[(3R,5S,6R)-6-(2,2-di-(fluoromethyl)propoxy)-5-methylmorpholin-3-yl]-propan-1-ol

Product 1

HCID 68558094(1S,2S)-2-Amino-3-(3-isopropylsulfanyl-5-fluorophenyl)-1-[(3R,5S,6R)-6-(2,2-di-(fluoromethyl)propoxy)-5-methylmorpholin-3-yl]-propan-1-olYield 58%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Heat a mixture of (1S,2S)-2-Amino-3-(3,5-difluorophenyl)-1-[(3R,5S,6R)-6-(2,2-di-(fluoromethyl)propoxy)-5-methylmorpholin-3-yl]-propan-1-ol (91 mg, 0.22 mol) and sodium 2-propanethiolate (328 mg, 3.34 mmol) in N-methylpyrrolidin-2-one (2.0 mL) at 90° C. in a sealed tube for 1 hour. Cool the reaction mixture to room temperature, dilute with methanol, add ammonium chloride (192 mg, 3.34 mmol), and mix well. Load mixture on SCX™ column and elute with 2.0 M ammonia in methanol to provide the desired compound (60 mg, 58%).

Workup

  1. temperatureHeat
  2. additionmix well
  3. washLoad mixture on SCX™ column and elute with 2.0 M ammonia in methanol

Sources & evidence

ORD record
ord-fee88246ea624d6cbfb0e92114619ab7
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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