Diethyl chlorophosphate → HCID 58557150, compound

HRID 1969520Notes

Reaction equation

HRID 1969520 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH:3]1[C:15]([O:17][CH2:18][CH3:19])=[O:16].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[P:30](Cl)(=[O:37])([O:34][CH2:35][CH3:36])[O:31][CH2:32][CH3:33]>CC(OC)(C)C>[CH2:32]([O:31][P:30]([O:1][C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:4][C:3]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16])([O:34][CH2:35][CH3:36])=[O:37])[CH3:33]

Participants

5

Reactant 3

HCID 13139Diethyl chlorophosphateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 64208761-(1,1-Dimethylethyl) 3-ethyl 4-oxo-1,3-piperidinedicarboxylate

Product 1

HCID 58557150HCID 58557150, compoundYield 49.5%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of 1-tert-butyl 3-ethyl 4-oxopiperidine-1,3-dicarboxylate (11.50 g, 42.4 mmol, ASDI) in MTBE (500 mL) at about −78° C. was added NaHMDS (1 M in THF, 53.0 mL, 53.0 mmol). After about 1 h, diethyl phosphorochloridate (7.62 mL, 53.0 mmol) was added to the reaction mixture. After about 30 min, the reaction mixture was allowed to warm to ambient temperature and stirred for about 16 h. The reaction mixture was partitioned between saturated aqueous NH4Cl (100 mL) and EtOAc (50 mL). The layers were separated. The aqueous layer was further extracted with EtOAc (2×50 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-100% EtOAc in heptane to yield 1-tert-butyl 3-ethyl 4-(diethoxyphosphoryloxy)-5,6-dihydropyridine-1,3(2H)-dicarboxylate (8.55 g, 49%) as a yellow oil: LC/MS (Table 1, Method b) Rt=2.35 min; MS m/z: 408 (M+H)+.

Workup

  1. waitAfter about 30 min
  2. customThe reaction mixture was partitioned between saturated aqueous NH4Cl (100 mL) and EtOAc (50 mL)
  3. customThe layers were separated
  4. extractionThe aqueous layer was further extracted with EtOAc (2×50 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customThe crude material was purified by silica gel chromatography
  8. washeluting with a gradient of 0-100% EtOAc in heptane

Sources & evidence

ORD record
ord-35871397af984cb59652e01995c5da8e
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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