chloromethyl 2-methylpropanoate

Additional information on environmental fate and behaviour

Administrative data

Endpoint:

additional information on environmental fate and behaviour

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

unsuitable test system

Data source

Reference

Reference Type:

publication

Title:

Effect of Acyl Chain Length and Branching on the Enantioselectivity of Candida rugosa Lipase in the Kinetic Resolution of 4-(2-Difluoromethoxyphenyl)-Substituted 1,4-Dihydropyridine 3,5-Diesters

Author:

Arkadij Sobolev, Maurice C. R. Franssen, Brigita Vigante, Brigita Cekavicus, Raivis Zhalubovskis, Huub Kooijman, Anthony L. Spek, Gunars Duburs, and Aede de Groot†

Year:

2002

Bibliographic source:

J. Org. Chem. 2002, 67, 401-410

Materials and methods

GLP compliance:

not specified

Test material

Test material information

Results and discussion

Any other information on results incl. tables

See Scheme 1 of the publication describes the synthesis of dihydropyridine substrates with the use of e.g., chloromethyl isobutyrate.

3-[(Isobutyryloxy)methyl] 5-(2-Propoxyethyl) 4-[2-(Difluoromethoxy) phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (6c).

This compound was prepared via the same method used for compound 6a. Beginning with 957 mg (2 mmol) of 4a, 135 mg (2.4 mmol) of KOH, and 355 mg (2.6 mmol) of isobutyryloxymethyl chloride, 6c was obtained in 72% (762 mg).

3-[(Isobutyryloxy)methyl] 5-Methyl 4-[2-(Difluoromethoxy) phenyl]-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (6f).

To a solution of 3.00 g (8.5 mmol) of 5b in 6 mL of dry DMF was added 1.41 g (10.2 mmol) of K2CO3 at room temperature, and the reaction mixture was stirred for 2 h, after which 1.50 g (11.0 mmol) of isobutyryloxymethyl chloride was added. The mixture was stirred overnight, diluted with CHCl3, washed with water (three times) and brine, dried over MgSO4, and evaporated. The remaining residue was flash chromatographed on silica gel with petroleum ether (bp 40 - 60 °C)/ethyl acetate (2:1) followed by crystallization from ethanol to give 2.67 g (71%) of 6f as white crystals.

Applicant's summary and conclusion

Executive summary:

Since the introduced reaction of Chloromethyl isobutyrate is unlikely to be relevant in the environment, this reaction is considered to be of linited relevance for the environmental risk assesment. Hence, this study is disregarded.