1,4-Dichlorobenzene → Methyl 2,5-difluoro-3-methylbenzoate

HRID 655937Notes

Reaction equation

HRID 655937 reaction equation
N[C:2]1[C:11]([CH3:12])=[CH:10][C:9]([F:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:14][B-](F)(F)F.N#[O+].C1C(Cl)=CC=C(Cl)C=1>C(Cl)Cl>[F:14][C:2]1[C:11]([CH3:12])=[CH:10][C:9]([F:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

5

Reactant 3

HCID 46851,4-DichlorobenzeneHCID 11137142Nitrilooxonium tetrafluoroborateHCID 53415135Methyl 2-amino-5-fluoro-3-methylbenzoate

Product 1

HCID 55264253Methyl 2,5-difluoro-3-methylbenzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (E3) (1.0 eq.) in dry DCM (0.4 M) at 0° C. was added nitrosonium tetrafluoroborate (1.3 eq.) portionwise. After 1 h at 0° C. dry dichlorobenzene (120 eq.) was added and the reaction was slowly heated to 160° C. while DCM was distilled off. After 3 hrs, the mixture was cooled to RT, EtOAc was added and the organic phase was washed with brine (2×). After drying over MgSO4, the solvents were removed under reduced pressure. The crude was purified by flash chromatography using 1-10% EtOAc/petroleum ether to yield (E4) as a yellow oil. 1H NMR (400 MHz, CDCl3, 300K) δ 7.42 (1H, m), 7.06 (1H, m), 3.92 (3H, s), 2.30 (3H, d, J=2.3 Hz).

Workup

  1. distillationwas distilled off
  2. additionEtOAc was added
  3. washthe organic phase was washed with brine (2×)
  4. dry with materialAfter drying over MgSO4
  5. customthe solvents were removed under reduced pressure
  6. customThe crude was purified by flash chromatography

Sources & evidence

ORD record
ord-e8be6a48271c432988bb96357fd2df99
Source dataset
uspto-grants-2011_12
Patent number
US08071623B2

Reaction notes

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