Diisopropylamine → isobutyl P-(3-t-butoxycarbonylamino-2-oxo-propyl)-P-(methyl)-phosphinate

HRID 865846Notes

Reaction equation

HRID 865846 reaction equation
C(N[CH:5]([CH3:7])C)(C)C.C([Li])CCC.[CH3:13][P:14]([CH3:21])(=[O:20])[O:15][CH2:16][CH:17]([CH3:19])[CH3:18].[C:22]([O:26][C:27]([NH:29]NCC(OC)=O)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(=O)(O)[O-:37].[Na+]>O1CCCC1.CCCCCC.C(O)(=O)C>[C:22]([O:26][C:27]([NH:29][CH2:7][C:5](=[O:37])[CH2:13][P:14]([CH3:21])(=[O:20])[O:15][CH2:16][CH:17]([CH3:19])[CH3:18])=[O:28])([CH3:23])([CH3:24])[CH3:25]

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 516892Sodium BicarbonateHCID 4188612isobutyl P,P-dimethyl-phosphinateHCID 12031831Hydrazinecarboxylic acid, 2-(2-methoxy-2-oxoethyl)-, 1,1-dimethylethyl esterHCID 178418339Butyllithium

Product 1

HCID 23374770isobutyl P-(3-t-butoxycarbonylamino-2-oxo-propyl)-P-(methyl)-phosphinate

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

To a solution of 6.1 g of diisopropylamine in 25 ml of dry tetrahydrofuran at 0° under an atmosphere of nitrogen are added 37.5 ml of a 1.6M solution of n-butyllithium in hexane. This solution is stirred for a period of 10 minutes and then cooled to -78°. To this is added, via a syringe, a solution of 9.0 g of isobutyl P,P-dimethyl-phosphinate in 50 ml of dry tetrahydrofuran and the mixture is stirred at -78° for a period of 1 hour. To this is then added a solution of 1.9 g of methyl N-tert.-butoxycarbonylaminoglycinate in 25 ml of dry tetrahydrofuran and the reaction mixture is allowed to warm to room temperature and is stirred for a period of 1 hour. 3 ml of glacial acetic acid are then introduced, followed by 50 ml of saturated sodium bicarbonate solution, and the aqueous layer is extracted twice with 100 ml of ether. The organic extract is dried over magnesium sulphate and concentrated under reduced pressure. The residue is chromatographed on silica gel using ethyl acetate as eluent. There is obtained isobutyl P-(3-t-butoxycarbonylamino-2-oxo-propyl)-P-(methyl)-phosphinate, m.p. 65°-68°, 31P-NMR spectrum: δ=+44.9 ppm (CDCl3).

Workup

  1. temperaturecooled to -78°
  2. additionTo this is added, via a syringe
  3. stirringis stirred for a period of 1 hour
  4. extractionthe aqueous layer is extracted twice with 100 ml of ether
  5. extractionThe organic extract
  6. dry with materialis dried over magnesium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is chromatographed on silica gel

Sources & evidence

ORD record
ord-2de8c33a3a894eb4bf2a2baf38686234
Source dataset
uspto-grants-1996_10
Patent number
US05567840

Reaction notes

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