2,6-Lutidine → (R)-methyl(1-phenylethyl)phosphoramidic dichloride

HRID 923717Notes

Reaction equation

HRID 923717 reaction equation
[P:1]([Cl:5])(Cl)([Cl:3])=[O:2].N1C(C)=CC=CC=1C.[CH3:14][NH:15][C@H:16]([CH3:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(Cl)Cl>[CH3:14][N:15]([C@@H:16]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:23])[P:1]([Cl:5])([Cl:3])=[O:2]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 2060888(R)-(+)-N-Methyl-1-phenylethylamine

Product 1

HCID 86663092(R)-methyl(1-phenylethyl)phosphoramidic dichlorideYield 54.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a cooled (ice/water bath) solution of phosphorus oxychloride (2.83 mL, 30.3 mmol) in DCM (30 mL) was added sequentially, dropwise, and with stirring 2,6-lutidine (7.06 mL, 60.6 mmol) and a DCM solution of (R)-(+)-N,a-dimethylbenzylamine (3.73 g, 27.6 mmol). After 5 minutes, the bath was removed and reaction mixture allowed to warm to ambient temperature. After 1 hour, the reaction solution was washed with a citric acid solution (50 mL×3, 10% w/v aq), dried (MgSO4), filtered through SiO2 and concentrated to provide the title compound (3.80 g) as a white foam. ESI/MS calcd. for 1-(4-nitrophenyl)piperazine derivative C19H25N4O4P 404.2, found m/z=403.1 (M−1).

Workup

  1. additionwas added sequentially
  2. customthe bath was removed
  3. customreaction mixture
  4. waitAfter 1 hour
  5. washthe reaction solution was washed with a citric acid solution (50 mL×3, 10% w/v aq)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered through SiO2
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-ee7b7fd5bbb4462b9df1b9d2bf03cacf
Source dataset
uspto-grants-2016_03
Patent number
US09278987B2

Reaction notes

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