Phosphorus oxychloride → 1,4-Difluoro-2-(isocyano(tosyl)methyl)benzene

HRID 1929966Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:13]([C:16]1[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=1)(=[O:15])=[O:14])[NH:10][CH:11]=O.P(Cl)(Cl)(Cl)=O>COCCOC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([N+:10]#[C-:11])[S:13]([C:16]1[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=1)(=[O:14])=[O:15]

Participants

Conditions

Temperature: -5 °C

Procedure

To a solution of N-((2,5-difluorophenyl)(tosyl)methyl)formamide (5.92 g, 18.2 mmol) in DME (100 mL) at about −10° C. was added phosphorus oxychloride (Fluka, 5.09 mL, 54.6 mmol) followed by dropwise addition of TEA (12.7 mL, 91.0 mmol) in DME (10 mL). The reaction mixture was stirred at about −5° C. for about 3 h. The reaction mixture was poured into ice-cold water (250 mL) and extracted with EtOAc (3×50 mL). The organic layer was dried with MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography using heptane/EtOAc (gradient; 1:0 to 1:1) to give the title compound (1.90 g, 34.0%) as a yellow solid. LC/MS (Table 1, Method a) Rt=2.94 min; MS m/z: 306.1 (M−H)−.

Workup

extractionextracted with EtOAc (3×50 mL)
dry with materialThe organic layer was dried with MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record: ord-a00b41f5a04d46bc83143542f0b67a4a
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188083B2

Reaction notes

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