Diisopropylethylamine → Tert-butyl 3-{[(dimethylphosphoryl)oxy]methyl}azetidine-1-carboxylate

HRID 410490Notes

Reaction equation

HRID 410490 reaction equation
C(N(C(C)C)CC)(C)C.[OH:10][CH2:11][CH:12]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1.[CH3:23][P:24](Cl)([CH3:26])=[O:25]>ClCCl.O>[CH3:23][P:24]([O:10][CH2:11][CH:12]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1)([CH3:26])=[O:25]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 517954Dimethylphosphinic chlorideHCID 10583745tert-Butyl 3-(hydroxymethyl)azetidine-1-carboxylate

Product 1

HCID 67431958Tert-butyl 3-{[(dimethylphosphoryl)oxy]methyl}azetidine-1-carboxylateYield 69.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Diisopropyl ethyl amine (124.28 g, 0.961 mol) was added dropwise to stirred solution of compound tert-butyl 3-(hydroxymethyl)azetidine-1-carboxylate (150 g, 0.80 mol) in dichloromethane (500 mL) at 0° C. Dimethyl phosphinyl chloride (90 g, 0.80 mol) in dichloromethane (300 mL) was added to above reaction mixture over a period of 90 min at same temperature. Then, the reaction mixture was warmed to room temperature and continued stirring for 2 h. After completion of the reaction, the mixture was diluted with water (300 mL). The layers were separated. The organic layer was washed with brine (300 ml), dried over sodium sulfate and concentrated. The resultant concentrated product was purified via column chromatography on silica gel using chloroform/methanol (95/5) to afford tert-butyl 3-{[(dimethylphosphoryl)oxy]methyl}azetidine-1-carboxylate (146.8 g, 68.3%) as brown liquid.

Workup

  1. customAfter completion of the reaction
  2. customThe layers were separated
  3. washThe organic layer was washed with brine (300 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe resultant concentrated product was purified via column chromatography on silica gel

Sources & evidence

ORD record
ord-2769a50fc53f43c2965f1d6307bf0cdb
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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