Phosphorus oxychloride → HCID 178472264, compound

HRID 1912611Notes

Reaction equation

HRID 1912611 reaction equation
[F:1][C:2]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:3]=1[CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][C:6]1=O.O=P(Cl)(Cl)Cl.[NH2:21][C:22](=[C:24]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH3:23].C([O-])(O)=O.[Na+].O>ClCCCl>[F:1][C:2]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:3]=1[CH2:4][N:5]1[CH2:9][CH2:8][CH2:7]/[C:6]/1=[N:21]\[C:22](=[C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH3:23]

Participants

6

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 15648022Diethyl 2-(1-aminoethylidene)malonateHCID 712090031-(2,3-Difluorobenzyl)pyrrolidin-2-oneHCID 86585896Sodium bicarbonate water

Product 1

HCID 178472264HCID 178472264, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 1-(2,3-difluorobenzyl)pyrrolidin-2-one (17.05 mL, 89 mmol) in 1,2-dichloroethane (DCE) (240 mL) under nitrogen atmosphere was added dropwise in 15 min POCl3 (12.39 mL, 133 mmol) and the mixture was stirred at ambient temperature for 1 h. Then diethyl 2-(1-aminoethylidene)malonate (19.62 g, 97 mmol) was added and the mixture was heated to 40° C. under nitrogen atmosphere for 22 h. Saturated NaHCO3/water was carefully added (400 mL) and the mixture was stirred at ambient temperature for 1 h then extracted with dichloromethane. The aqueous phase was extracted with dichloromethane and the combined organic phase was washed brine, dried (Na2SO4), concentrated, dried in vacuo to provide (E)-diethyl 2-(1-((1-(2,3-difluorobenzyl)pyrrolidin-2-ylidene)amino)ethylidene)malonate (36.48 g, 70.3 mmol, 79% yield) as a yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.07-1.36 (m, 6 H), 1.88-2.10 (m, 2 H), 2.18-2.27 (m, 3 H), 2.35-2.61 (m, 2 H), 3.13-3.43 (m, 2 H), 3.98-4.30 (m, 4 H), 4.45-4.64 (m, 2 H), 6.94-7.20 (m, 3 H); LCMS (m/z) ES+=395 (M+1).

Workup

  1. temperaturethe mixture was heated to 40° C. under nitrogen atmosphere for 22 h
  2. stirringthe mixture was stirred at ambient temperature for 1 h
  3. extractionthen extracted with dichloromethane
  4. extractionThe aqueous phase was extracted with dichloromethane
  5. washthe combined organic phase was washed brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customdried in vacuo

Sources & evidence

ORD record
ord-ddbd2c64d68448d89528c378e911dcf0
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

Loading…