Phosphorus oxide (P4O10) → 2,5-Difluoro-2',6-dimethyl-4',5',6'-trimethoxybenzophenone

HRID 896846Notes

Reaction equation

HRID 896846 reaction equation
[F:1][C:2]1[C:3]([CH3:12])=[C:4]([C:8]([F:11])=[CH:9][CH:10]=1)[C:5]([OH:7])=O.[CH3:13][O:14][C:15]1[CH:16]=[C:17]([CH3:25])[CH:18]=[C:19]([O:23][CH3:24])[C:20]=1[O:21][CH3:22].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.COC(OC)(OC)C1C=CC=CC=1>O.ClCCl>[F:11][C:8]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([CH3:12])[C:4]=1[C:5]([C:18]1[C:19]([O:23][CH3:24])=[C:20]([O:21][CH3:22])[C:15]([O:14][CH3:13])=[CH:16][C:17]=1[CH3:25])=[O:7]

Participants

7

Reactant 4

HCID 14812Phosphorus oxide (P4O10)2×HCID 69720Trimethyl orthobeznoateHCID 809223,4,5-TrimethoxytolueneHCID 223525773,6-Difluoro-2-methylbenzoic acid

Product 1

HCID 223525782,5-Difluoro-2',6-dimethyl-4',5',6'-trimethoxybenzophenoneYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

9.3 g (54.3 mmol) of 3,6-difluoro-2-methylbenzoic acid and 9.88 g (54.3 mmol) of 3,4,5-trimethoxytoluene were introduced into 250 ml of absolute dichloromethane, and 54 g (380 mmol) of pulverulent phosphorus pentoxide were then added. The mixture was stirred for 16 hours at room temperature. According to HPLC check, the trimethoxytoluene had not been reacted completely. A further 13.5 g of phosphorus pentoxide were added. After a further four hours, the reaction mixture was poured into water and extracted with dichloromethane. The combined organic phases were then dried and concentrated. The crude product was purified by reversed-phase MPLC (eluent acetonitrile/water 7:3). This gave 12.2 g of the compound I.5-02 (36 mmol, 67% yield).

Workup

  1. additionwere then added
  2. waitAfter a further four hours
  3. extractionextracted with dichloromethane
  4. customThe combined organic phases were then dried
  5. concentrationconcentrated
  6. customThe crude product was purified by reversed-phase MPLC (eluent acetonitrile/water 7:3)

Sources & evidence

ORD record
ord-b835810b725742e1ac17c59a831a19a2
Source dataset
uspto-grants-2005_07
Patent number
US06919485B2

Reaction notes

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