Hydrochloric Acid → 3,3-Difluoro-2-trifluoromethyl-2,3,3a,4,5,6,7,7a-octahydrobenzofuran-2,3a-diol

HRID 491255Notes

Reaction equation

C([Li])CCC.[F:6][C:7]([F:15])([F:14])[CH:8]([OH:13])[C:9](F)([F:11])[F:10].Br[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][C:18]1=[O:23].Cl.[OH-:25].[Na+]>CCCCCC.O1CCCC1>[F:10][C:9]1([F:11])[C:18]2([OH:23])[CH2:19][CH2:20][CH2:21][CH2:22][CH:17]2[O:13][C:8]1([C:7]([F:15])([F:14])[F:6])[OH:25]

Participants

Conditions

Temperature: 5 °C

Procedure

In a nitrogen atmosphere at −5° C., 260 ml of 2.6M n-butyllithium in hexane was added to a mixture of 58 g of 1,1,1,3,3,3-hexafluoro-2-propanol and 260 g of tetrahydrofuran, followed by one hour of stirring at 5° C. Then 59 g of 2-bromocyclohexanone was added at 5° C. The mixture was stirred for 10 hours, after which dilute hydrochloric acid was added to quench the reaction and neutralize the reaction mixture. Then 310 g of a 10% aqueous solution of sodium hydroxide was added to the reaction mixture, from which an aqueous layer was separated. It was made acidic by adding 150 g of 20% dilute hydrochloric acid and combined with 250 g of toluene, after which separatory operation was performed to separate an organic layer. The organic layer was concentrated and purified by recrystallization from hexane, obtaining 58 g of the product (yield 72%).

Workup

stirringThe mixture was stirred for 10 hours
customto quench
customthe reaction
customwas separated
additionby adding 150 g of 20% dilute hydrochloric acid
customto separate an organic layer
concentrationThe organic layer was concentrated
custompurified by recrystallization from hexane

Sources & evidence

ORD record: ord-e8a426ca88db4e54ab78bc52ef379742
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07531289B2

Reaction notes

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