Phosphate → HCID 86739725, compound

HRID 1632944Notes

Reaction equation

HRID 1632944 reaction equation
[C:1]1([CH2:7][O:8][C:9]([NH:11][C@H:12]2[CH2:15][NH:14][C:13]2=[O:16])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.[P:22](Cl)(Cl)([O:24][CH3:25])=[O:23].[CH2:28]([NH2:31])[CH2:29][CH3:30].P([O-])([O-])([O-])=O>O1CCCC1.CCCCCC.C(#N)C>[C:1]1([CH2:7][O:8][C:9]([NH:11][CH:12]2[CH2:15][N:14]([P@@:22]([NH:31][CH2:28][CH2:29][CH3:30])(=[O:23])[O:24][CH3:25])[C:13]2=[O:16])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

9

Reactant 5

HCID 1061PhosphateHCID 7852PropylamineHCID 69611Methyl dichlorophosphateHCID 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamateHCID 178418339Butyllithium

Product 1

HCID 86739725HCID 86739725, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

(S)-3-[[(Phenylmethoxy)carbonyl]amino]-2-azetidinone (5.0 g) was dissolved in dry tetrahydrofuran (140 ml) and cooled to -78° C. in a dry ice-acetone bath under a nitrogen atmosphere. This mixture was treated with 1 equivalent of a 1.56 M solution of n-butyl lithium in hexane (14.2 ml) and was stirred for 30 minutes at -78° C. Methyl dichlorophosphate (3.38 g) was added and the mixture stirred for 1 hour at -78° C., followed by the addition of 2 equivalents of distilled n-propylamine (2.68 g) and stirring for an additional 2 hours at -78° C. The reaction was treated with 0.5 M phosphate buffer pH 5.5 (150 ml), allowed to warm to 5° C., and extracted with three 125 ml portions of ethyl acetate. The extracts were combined, dried over anhydrous Na2SO4 and the solvent removed in vacuo yielding an oily residue. The residue was dissolved in acetonitrile (60 ml) and applied to 500 g column of silica gel eluting with acetonitrile. Removal of solvent in vacuo yielded 4.6 g of the title compound, melting point 121°-123° C.

Workup

  1. stirringthe mixture stirred for 1 hour at -78° C.
  2. stirringstirring for an additional 2 hours at -78° C
  3. temperatureto warm to 5° C.
  4. extractionextracted with three 125 ml portions of ethyl acetate
  5. dry with materialdried over anhydrous Na2SO4
  6. customthe solvent removed in vacuo
  7. customyielding an oily residue
  8. customRemoval of solvent in vacuo

Sources & evidence

ORD record
ord-861e9bdf0515406bb6cd10b9a00760ee
Source dataset
uspto-grants-1984_10
Patent number
US04478749

Reaction notes

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