Acid to Acid Chloride

(COCl)₂

Examples:

Example 1

Alcohol to Ketone rxn1

To a suspension of the SM (0.3 g, 2.38 mmol) in DCM (10 mL) was added (COCl)2 (0.3 mL, 3.6 mmol) dropwise at 0 C. The resulting mixture was stirred at RT for 1 h then heated to 70 C for 2 h. After cooling to RT the excess (COCl)2 and solvent were removed in vacuo (at <40 C) to provide the product as a gum which was taken to the next step without further purification.

[Patent Reference: WO2010038081, page 138, (33.8 MB)]

Example 2

To a mixture of the SM (603 mg, 2.35 mmol) and DMF (1 drop) in DCM (10 mL) was added (COCl)2 (592 mg, 4.70 mmol) at RT. The reaction mixture was stirred at RT for 2 h. The mixture was concentrated to provide the product as a yellow solid which was taken to the next step without further purification. [600 mg, 93%]

[Patent Reference: WO2016011390, page 126, (20.2 MB)]

Example 3

To a stirred solution of DCM (50 mL) and DMF (0.50 mL) at 0 C was added dropwise (COCl)2 (4.6 mL, 54 mmol). The cooling bath was removed and stirring was continued for 10 min. To this mixture was added portionwise the SM (5.0 g, 27 mmol). The reaction mixture was stirred for an additional 2.5 h, after which time the solvent was removed in vacuo to provide the product which was used directly in the next step. [5.7 g]

[Patent Reference: WO2016014463, page 126, (6.7 MB)]