Water → HCID 15435120, compound

HRID 581232Notes

Reaction equation

HRID 581232 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:11]/[O:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)/[C:8]([OH:10])=[O:9])[N:6]=1.N12CCN(CC1)CC2.[P:27](Cl)([O:32][CH2:33][CH3:34])([O:29][CH2:30][CH3:31])=[S:28].O>CC(N(C)C)=O>[CH2:30]([O:29][P:27]([O:9][C:8](=[O:10])/[C:7](/[C:5]1[N:6]=[C:2]([NH2:1])[S:3][CH:4]=1)=[N:11]\[O:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][O:14]1)([O:32][CH2:33][CH3:34])=[S:28])[CH3:31]

Participants

6

Reactant 4

HCID 962WaterHCID 9237DabcoHCID 17305O,O-diethyl phosphorochloridothioateHCID 88204179HCID 88204179, compound

Product 1

HCID 15435120HCID 15435120, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
2 °C

Procedure

To a stirred suspension of 30 g (Z)-(RS)-(2-aminothiazol-4-yl)-[(tetrahydropyran-2-yloxyimino)]-acetic acid (80.5 mmol) and 90 mg 1,4-diazabicyclo[2.2.2]octane (DABCO) (0.80 mmol) in 300 ml dimethylacetamide was added under argon over 45 min 17 ml diethyl chlorothiophosphate (104.9 mmol). Stirring was continued at 0° C. for 1 h. The reaction was followed by HPLC. To the slightly turbid reaction mixture was added dropwise over 50 min 450 ml water. The precipitated product was filtered, washed with water and dissolved in dichloromethane. The aqueous layer was back-extracted with dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure until the product started to crystallize. To the residual solution was added dropwise over 30 min n-hexane. The resulting suspension was cooled to 2° C., stirred for 1 h and then filtered. The crystalline product was washed with n-hexane and dried to constant weight. (Z)-(RS)-(2-aminothiazol-4-yl)-[(tetrahydropyran-2-yloxyimino)]-acetic acid diethoxythio-phosphoryl ester was obtained as a white solid (28.01 g, yield=82%) and was stored under argon at -20° C. No further purificiation was necessary and the product was used as isolated for the next step.

Workup

  1. customTo the slightly turbid reaction mixture
  2. filtrationThe precipitated product was filtered
  3. washwashed with water
  4. dissolutiondissolved in dichloromethane
  5. extractionThe aqueous layer was back-extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure until the product
  8. customto crystallize
  9. additionTo the residual solution was added dropwise over 30 min n-hexane
  10. stirringstirred for 1 h
  11. filtrationfiltered
  12. washThe crystalline product was washed with n-hexane
  13. customdried to constant weight

Sources & evidence

ORD record
ord-5c9bfb6bca1a419b8f602c22cc702a3f
Source dataset
uspto-grants-1999_07
Patent number
US05919939

Reaction notes

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