Water → HCID 67357362, compound

HRID 884028Notes

Reaction equation

HRID 884028 reaction equation
[C:1]([N:5]([CH2:10][C@H:11]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)O)[CH2:6][CH2:7][C:8]#[N:9])([CH3:4])([CH3:3])[CH3:2].CCOP(Cl)(OCC)=O.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.O>C1COCC1>[C:1]([N:5]1[CH2:10][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[C@@H:7]([C:8]#[N:9])[CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 13139Diethyl chlorophosphateHCID 2733832Lithium HexamethyldisilazideHCID 67356870HCID 67356870, compound

Product 1

HCID 67357362HCID 67357362, compoundYield 10.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-{t-Butyl[(2S)-2-(4-chlorophenyl)-2-hydroxyethyl]-amino}propanenitrile (5 g, 17.80 mmol) prepared according to the process described in WO 2004/09126 was dissolved in THF (27 mL). The reaction mixture was cooled to −20° C. or less, to which was added chlorodiethylphosphate (2.69 ml, 18.70 mmol). The reaction temperature was maintained at 12˜18° C., during which 1M LHMDS (37.4 ml, 37.38 mmol) was added dropwise over 2 hours. After the reaction was completed, water (45 mL) was added while the temperature was maintained at 15° C. or less. The resulting mixture was stirred for 30 minutes and extracted with EtOAc. Thus extracted organic solution was concentrated in vacuo and purified by column chromatography (eluent: EtOAc/Hex=1/3) to give the title compound (0.5 g, 10.69%).

Workup

  1. temperatureThe reaction mixture was cooled to −20° C. or less, to which
  2. additionwas added dropwise over 2 hours
  3. temperaturewas maintained at 15° C. or less
  4. extractionextracted with EtOAc
  5. concentrationThus extracted organic solution was concentrated in vacuo
  6. custompurified by column chromatography (eluent: EtOAc/Hex=1/3)

Sources & evidence

ORD record
ord-58fad4565a094394bfb78af439284e83
Source dataset
uspto-grants-2012_08
Patent number
US08236955B2

Reaction notes

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