Hydrochloric Acid → 4,4,4-Trifluoro-2-methylbutanoic acid

HRID 1741907Notes

Reaction equation

C[Si](C)(C)N[Si](C)(C)C.[Na].[F:11][C:12]([F:21])([F:20])[CH2:13][CH2:14][C:15]([O:17]CC)=[O:16].[CH3:22]I.[OH-].[Li+].Cl>O1CCCC1.CO>[CH3:22][CH:14]([CH2:13][C:12]([F:21])([F:20])[F:11])[C:15]([OH:17])=[O:16]

Participants

Conditions

Temperature: 0 °C

Procedure

To sodium hexamethyldisilazane (0.945M in tetrahydrofuran) (667 mL, 0.63 mol) in tetrahydrofuran (0.9 L) at -78° C., under nitrogen, was added a solution of ethyl 4,4,4-trifluorobutyrate (90.6 mL) in tetrahydrofuran (100 mL). After stirring for 1.5 hour, to the vigorously stirred mixture was added methyl iodide (112 mL) as fast as possible. The reaction was warmed with a 0° C. bath for 2 hours. Methanol (1 L) and 1N lithium hydroxide (1.2 L) were added and stirring continued for 48 hours. The mixture was acidified with 2N hydrochloric acid and extracted with ethyl acetate. The combined organic phase was washed (brine), dried (MgSO4), and evaporated at 30° C. After combination with product from separate conversions of ethyl 4,4,4-trifluorobutyrate (97.79 g), distillation afforded 2-methyl-4,4,4-trifluorobutyric acid (173.24 g, 96%) as a brown solid-liquid contaminated with 4,4,4-trifluorobutyric acid and 2,2-dimethyl-4,4,4-trifluorobutyric acid; bp 48.0°-108° C. (9,900 Pa); GLC: tR =6.1 min.

Workup

stirringstirring
waitcontinued for 48 hours
extractionextracted with ethyl acetate
washThe combined organic phase was washed (brine)
dry with materialdried (MgSO4)
customevaporated at 30° C
customAfter combination with product from separate
distillationconversions of ethyl 4,4,4-trifluorobutyrate (97.79 g), distillation

Sources & evidence

ORD record: ord-57108b060196448096b7355aff0fca16
Source dataset: uspto-grants-1994_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05334765

Reaction notes

Loading…