Chlorotrimethylsilane → HCID 11151531, compound

HRID 492121Notes

Reaction equation

HRID 492121 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][CH2:15][NH:14][C:13]1=[O:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.C[Si](Cl)(C)C.[P:33](Cl)(Cl)(Cl)=[O:34].O.[NH3:39].[Cl-].[NH4+:41]>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][CH2:15][N:14]([P:33]([NH2:41])([NH2:39])=[O:34])[C:13]1=[O:18])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 6397ChlorotrimethylsilaneHCID 24813Phosphorus oxychlorideHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 11482034Benzyl [(3S)-2-oxopiperidin-3-yl]carbamateHCID 12896473Azane;hydrate2×

Product 1

HCID 11151531HCID 11151531, compoundYield 43.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

600 g (2.42 mol) of (S)-3-benzyloxycarbonylamino-2-piperidone was added to 6 L of toluene and 823 mL (4.80 mol) of diisopropylethylamine, subsequently 612 mL (4.80 mol) of trimethylsilyl chloride was added dropwise, and the solution was stirred at room temperature for 24 hours. Subsequently, 894 mL (9.60 mol) of phosphorus oxychloride was added dropwise, and the solution was stirred at room temperature for 48 hours. An ammonia water adjusted to a pH of about 10 with ammonium chloride was cooled to −10° C. or lower, and the reacted solution was added dropwise into it. When the pH falls to less than 9, the ammonia water was added. The obtained suspension was filtered, and the residue was washed with 3 L of toluene, subsequently 2 L of a toluene-THF mixed solvent, and then extracted with 10 L of a THF-methanol mixed solvent. The extracted liquid was vacuum-concentrated, the residue was washed with 6 L of water and suspension-purified with 10 L of an ethanol-diisopropylether mixed solvent, and 345.7 g of (S)-3-benzyloxycarbonylamino-1-diamino phosphinyl-2-piperidone (1.06 mol and a yield of 43.8%) was obtained.

Workup

  1. additionwas added dropwise
  2. stirringthe solution was stirred at room temperature for 48 hours
  3. temperaturewas cooled to −10° C.
  4. additionlower, and the reacted solution was added dropwise into it
  5. filtrationThe obtained suspension was filtered
  6. washthe residue was washed with 3 L of toluene, subsequently 2 L of a toluene-THF mixed solvent
  7. extractionextracted with 10 L of a THF-methanol mixed solvent
  8. concentrationThe extracted liquid was vacuum-concentrated
  9. washthe residue was washed with 6 L of water
  10. customsuspension-purified with 10 L of an ethanol-diisopropylether mixed solvent, and 345.7 g of (S)-3-benzyloxycarbonylamino-1-diamino phosphinyl-2-piperidone (1.06 mol
  11. customa yield of 43.8%) was obtained

Sources & evidence

ORD record
ord-2c841d05a26b4bae9704ca9a20a165b9
Source dataset
uspto-grants-2009_05
Patent number
US07531657B2

Reaction notes

Loading…