Oxalyl chloride → 2-(4-Fluorophenyl)acetyl isocyanate

Temperatur

80 °C

To a solution/suspension of 4-fluorophenylacetamide (77 mg, 0.50 mmol, see generally, J. Med. Chem. 2003, 46, 4333–4341, the disclosure of which is herein incorporated by referene) in dichloroethane (2 mL) was added oxalyl chloride (0.175 mL, 2.00 mmol). The reaction was heated at 80° C. for 24 h and then 70° C. for two days. By this time, most of the solids had dissolved and the reaction was yellow. LC/MS analysis found a peak with a molecular weight of 211 corresponding to methyl 2-(4-fluorophenyl)acetylcarbamate, resulting from quenching of the isocyanate with methanol. The reaction was concentrated in vacuo to give a yellow slurry. The slurry was redissolved in dichloroethane (2 mL) and again concentrated in vacuo. The resulting residue was redissolved again in dichloroethane (2 mL) to give a 0.25 M solution of 2-(4-fluorophenyl)acetyl isocyanate in dichloroethane, which was used directly in subsequent reactions.

1. dissolutionBy this time, most of the solids had dissolved
2. customresulting
3. customfrom quenching of the isocyanate with methanol
4. concentrationThe reaction was concentrated in vacuo
5. customto give a yellow slurry
6. concentrationagain concentrated in vacuo
7. dissolutionThe resulting residue was redissolved again in dichloroethane (2 mL)

ORD-Eintrag

ord-e5f6a37655cf4913948ca2542b9b0a51

Quelldatensatz

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07173031B2