Sodium Carbonate → (1R)-(+)-(1-benzyloxycarbonylamino-2-methylpropyl)phosphonic acid

HRID 490934Notes

Reaction equation

HRID 490934 reaction equation
[NH2:1][C@H:2]([P:6](=[O:9])([OH:8])[OH:7])[CH:3]([CH3:5])[CH3:4].C([O-])(O)=O.[Na+].C([O-])([O-])=O.[Na+].[Na+].[CH2:21]([O:28][C:29](Cl)=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>[OH-].[Na+].O>[CH2:21]([O:28][C:29]([NH:1][C@H:2]([P:6](=[O:8])([OH:7])[OH:9])[CH:3]([CH3:5])[CH3:4])=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 10387Benzyl chloroformate2×HCID 516892Sodium BicarbonateHCID 27348871-Amino-2-methylpropylphosphonic acid, (R)-

Product 1

HCID 67375341(1R)-(+)-(1-benzyloxycarbonylamino-2-methylpropyl)phosphonic acidYield 91.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 14798Sodium HydroxideSolvent2×

Procedure

A slurry of (1R)-(+)-(1-amino-2-methylpropyl)phosphonic acid (2.57 g, 16.8 mmol), NaHCO3 (2.82 g, 33.6 mmol), and Na2CO3 (3.58 g, 33.8 mmol) in 16 mL of 2N NaOH and 3 mL of H2O was cooled in an ice water bath. To this was added benzyloxycarbonyl chloride (2.4 mL, 16.8 mmol). During the next 2 hours, two additional aliquots of benzyloxycarbonyl chloride were added (2.4 mL each). After stirring at ambient temperature for 16 hours, 40 mL of 2N NaOH was added and the mixture was partitioned between water and ether. The aqueous portion was washed with ether, acidified to pH 2 with concentrated HCl, and extracted with ethyl acetate (2×) and with methylene chloride (2×). The combined organic extracts were washed with saturated NaCl, dried over MgSO4, filtered, and concentrated in vacuo to give 4.41 g (91%) of (1R)-(+)-(1-benzyloxycarbonylamino-2-methylpropyl)phosphonic acid as a white foam.

Workup

  1. customthe mixture was partitioned between water and ether
  2. washThe aqueous portion was washed with ether
  3. extractionextracted with ethyl acetate (2×) and with methylene chloride (2×)
  4. washThe combined organic extracts were washed with saturated NaCl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2d3208f23dfb421b97cecf5e1a8400ed
Source dataset
uspto-grants-2009_05
Patent number
US07528173B2

Reaction notes

Loading…