Diisopropylethylamine → (4S,5R)-4-(3,4-difluorophenyl)-5-methoxymethyl-2-oxo-oxazolidine-3-carboxylic acid {3-[4-(2-cyanophenyl)piperidin-1-yl]propyl}amide hydrochloride

HRID 1976608Notes

Reaction equation

HRID 1976608 reaction equation
[N+](C1C=CC(O[C:11]([N:13]2[C@@H:17]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[C:20]([F:25])[CH:19]=3)[C@H:16]([CH2:26][O:27][CH3:28])[O:15][C:14]2=[O:29])=[O:12])=CC=1)([O-])=O.[ClH:30].Cl.[NH2:32][CH2:33][CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][CH:39]([C:42]2[CH:49]=[CH:48][CH:47]=[CH:46][C:43]=2[C:44]#[N:45])[CH2:38][CH2:37]1.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C>[ClH:30].[C:44]([C:43]1[CH:46]=[CH:47][CH:48]=[CH:49][C:42]=1[CH:39]1[CH2:38][CH2:37][N:36]([CH2:35][CH2:34][CH2:33][NH:32][C:11]([N:13]2[C@@H:17]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[C:20]([F:25])[CH:19]=3)[C@H:16]([CH2:26][O:27][CH3:28])[O:15][C:14]2=[O:29])=[O:12])[CH2:41][CH2:40]1)#[N:45]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 183266262-[1-(3-Aminopropyl)piperidin-4-yl]benzonitrile dihydrochlorideHCID 70243644(4S,5R)-4-(3,4-difluorophenyl)-2-oxo-5-methoxymethyl-oxazolidine-3-carboxylic acid 4-nitrophenyl ester

Product 1

HCID 86756684(4S,5R)-4-(3,4-difluorophenyl)-5-methoxymethyl-2-oxo-oxazolidine-3-carboxylic acid {3-[4-(2-cyanophenyl)piperidin-1-yl]propyl}amide hydrochloride

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (4S,5R)-4-(3,4-difluorophenyl)-2-oxo-5-methoxymethyl-oxazolidine-3-carboxylic acid 4-nitrophenyl ester (195 mg, 0.48 mmol) in dry tetrahydroftirin (3 mL) was added 2-[1-(3-aminopropyl)piperidin-4-yl]benzonitrile dihydrochloride (134 mg, 0.48 mmol) (see Example 3) followed by N,N-diisopropylethylamine (167 μL, 0.96 mmol). The reaction mixture was stirred at room temperature for 20 h when the reaction was diluted with ethyl acetate (50 mL), washed with 10% aqueous sodium carbonate solution (6×25 mL), dried over magnesium sulfate and filtered. The volatiles were removed under reduced pressure and the resulting oil was purified by pressurized silica gel chromatography (2% methanol in ethyl acetate) to afford an oil. The hydrochloride salt was prepared by standard procedures to provide (4S,5R)-4-(3,4-difluorophenyl)-5-methoxymethyl-2-oxo-oxazolidine-3-carboxylic acid {3-[4-(2-cyanophenyl)piperidin-1-yl]propyl}amide hydrochloride as a white solid.

Workup

  1. washwashed with 10% aqueous sodium carbonate solution (6×25 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. customThe volatiles were removed under reduced pressure
  5. customthe resulting oil was purified by pressurized silica gel chromatography (2% methanol in ethyl acetate)
  6. customto afford an oil

Sources & evidence

ORD record
ord-661e2016fd0041c39bdb10e3189321a3
Source dataset
uspto-grants-2001_05
Patent number
US06228870B1

Reaction notes

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