Diphenyl chlorophosphate → HCID 178503450, compound

HRID 1583520Notes

Reaction equation

HRID 1583520 reaction equation
[OH:1][C@@H:2]([C@H:4]1[C:10](=[O:11])[N:9]2[C@@H:5]1[CH2:6][C:7](=O)[CH:8]2[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1)=[O:13])[CH3:3].C(N(C(C)C)CC)(C)C.[P:35](Cl)([O:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)([O:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:36].FC(F)(F)S([O-])(=O)=O.[CH3:60][S:61][C:62]1[N:66]([CH3:67])[CH:65]=[CH:64][N+:63]=1[CH2:68][CH2:69][SH:70]>C(#N)C.O>[C:38]1([O:37][P:35]([O-:1])([O:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:36])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[CH3:60][S:61][C:62]1[N:66]([CH3:67])[CH:65]=[CH:64][N+:63]=1[CH2:68][CH2:69][S:70][C:7]1[CH2:6][C@H:5]2[N:9]([C:10](=[O:11])[C@@H:4]2[C@H:2]([OH:1])[CH3:3])[C:8]=1[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1)=[O:13]

Participants

7

Reactant 4

HCID 75654Diphenyl chlorophosphateHCID 81531Diisopropylethylamine2×HCID 11198839(4-Nitrophenyl)methyl (5R,6S)-6-((1R)-1-hydroxyethyl)-3,7-dioxo-1-azabicyclo(3.2.0)heptane-2-carboxylateHCID 178503451HCID 178503451, compound

Product 1

HCID 178503450HCID 178503450, compoundYield 58.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

To a solution of p-nitrobenzyl (5R, 6S)-6-[1-(R)-hydroxyethyl]-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate (1.40 g, 4.0 mmol) in 50 mL of dry acetonitrile, at 0° C. under N2, was added dropwise diisopropylethylamine (0.76 mL, 4.4 mmol) followed by diphenyl chlorophosphate (0.91 mL, 4.1 mmol). After stirring the reaction mixture at room temperature for 1 h, diisopropylethylamine (0.76 mL, 4.4 mmol) was added and then a solution of 2-methylthio-3-methyl-1-(2-mercaptoethyl)imidazolium trifluoromethanesulfonate (2.0 g, 5.9 mmol) in 5 mL of acetonitrile was added dropwise. The reaction mixture was kept at room temperature for 1.5 h and was then concentrated in vacuo to give a gum. This gum was taken up in H2O and applied to a C18 reverse-phase column. Elution with H2O, then 20% acetonitrile-H2O and finally 30% acetonitrile-H2O, followed by lyophilization of the appropriate fractions afforded the product (0.90 g, 30%) as a light yellow solid. ir(KBr) νmax : 3380 (br, OH), 1770 (β-lactam CO) cm-1 ; 'Hnmr (d6 -acetone) δ: 8.35 (br s, 1H), 8.24, 7.78 (AB q, J=8.8 Hz, 4H, aromatic), 7.89 (br s, 1H), 7.25-6.91 (m, 10H, diphenylphosphate), 5.50, 5.25 (ABq, J=12 Hz, 2H, benzylic), 4.75-4.27 (m, 3H), 4.03 (s, 3H, N-Me), 4.15-2.75 (m, 8H), 2.53 (s, 3H, S-Me), 1.22 (d, J=6.2 Hz, 3H, --CHMe).

Workup

  1. waitThe reaction mixture was kept at room temperature for 1.5 h
  2. concentrationwas then concentrated in vacuo
  3. customto give a gum
  4. washElution with H2O

Sources & evidence

ORD record
ord-c4b5b43134774a7b8b86086833065286
Source dataset
uspto-grants-1985_11
Patent number
US04552696

Reaction notes

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