Benzophenone → Ethyl 2-(diphenylmethyleneamino)acetate

HRID 1744035Notes

Reaction equation

HRID 1744035 reaction equation
[C:1]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:16]([O:18][C:19](=[O:22])[CH2:20][NH2:21])[CH3:17].B(F)(F)F.CCOCC.C(N(CCCC)CCCC)CCC>O.C1(C)C=CC=CC=1>[CH2:16]([O:18][C:19](=[O:22])[CH2:20][N:21]=[C:1]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH3:17]

Participants

7

Reactant 4

HCID 3102Benzophenone2×HCID 7622TributylamineHCID 8000Boron trifluoride etherateHCID 2723640Glycine ethyl ester, hydrochloride

Product 1

HCID 319508Ethyl 2-(diphenylmethyleneamino)acetate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

To a 250 mL round bottom flask, was added 5.52 g of benzophenone (1 eq), 8.46 g of glycine ethyl ester hydrochloride (1, 2 eq), 67 mL of toluene, and a trace amount of BF3.Et2O. The slurry was heated to reflux (112˜113° C.). Tributylamine (11.2 g) was then added dropwise over 120 min. The reaction mixture was stirred at reflux (114–116° C.) until the area percent (AP) of benzophenone <9.0% by HPLC (22–29 h). The reaction mixture was cooled to 15–25° C. and water (35 mL) was added. After phase separation, the organic phase was concentrated to 50% (w/w) under reduced pressure at <40°. The concentrated solution was then cooled to 20° C., followed by addition of methanol (3 mL). The slurry was cooled to 10° C. and stirred for 30 min. The resultant slurry was filtered. The wet cake was washed with cold water/methanol (5:1 v/v, 2×20 mL), and dried under vacuum at 20° C. for 24 h to give N-(diphenylmethylene)glycine ethyl ester (2) as an off-white to yellow solid (5.5 g, 95% pure by HPLC, 65.6% isolated yield). 1H NMR (CDCl3): δ 1.27 (t, J=7.25 Hz, 3H), 4.20 (s, 2H), 4.20 (q, J=7.07, 2H), 7.17–7.67 (m, 10H). Preparation of Ethyl 2-(diphenylmethylene)amino-2-difluoromethyl-4-cyanobutanoate from N-(Diphenylmethylene)glycine Ethyl Ester (R1=CH3CH2, R2=Ph)

Workup

  1. temperatureThe slurry was heated
  2. temperatureto reflux (112˜113° C.)
  3. temperatureThe reaction mixture was cooled to 15–25° C.
  4. customAfter phase separation
  5. concentrationthe organic phase was concentrated to 50% (w/w) under reduced pressure at <40°
  6. additionfollowed by addition of methanol (3 mL)
  7. temperatureThe slurry was cooled to 10° C.
  8. stirringstirred for 30 min
  9. filtrationThe resultant slurry was filtered
  10. washThe wet cake was washed with cold water/methanol (5:1 v/v, 2×20 mL)
  11. customdried under vacuum at 20° C. for 24 h

Sources & evidence

ORD record
ord-fc89e0cd3fde42d281972eedb98cbd81
Source dataset
uspto-grants-2006_03
Patent number
US07012158B2

Reaction notes

Loading…