Boron trifluoride → (3R-cis)-5-(2,4-difluorophenyl)tetrahydro-5-(iodomethyl)-3-furanmethanol

HRID 512806Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([CH2:17][I:18])[O:13][CH2:12][C@@H:11]([C:14](O)=[O:15])[CH2:10]1.[BH4-].[Na+].B(F)(F)F>O1CCCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([CH2:17][I:18])[O:13][CH2:12][C@@H:11]([CH2:14][OH:15])[CH2:10]1

Participants

Conditions

Temperature: 27.5 °C

Procedure

A solution of (3S,5R)-5-(2,4-difluorophenyl)-5-(iodomethyl)tetrahydrofuran-3-carboxylic acid compound of formula-7 (150 g) in tetrahydrofuran (750 ml) was added to a pre-cooled solution of sodium borohydride (45.2 g) in tetrahydrofuran (750 ml) at 0-5° C., followed by BF3-etherate (172.29 g) at 0-5° C. Temperature of the reaction mixture was raised to 25-30° C. and stirred for 2 hours at the same temperature. After completion of the reaction, the reaction mixture was quenched with 5% aqueous hydrochloric acid. Added ethylacetate to the reaction mixture. Both organic and aqueous layers were separated and the aqueous layers were extracted with ethyl acetate. Both the organic layers were combined, washed with water followed by 10% sodium chloride solution and then distilled off the solvent to get the title compound as a residue. Yield: 140 g; purity by HPLC: 98.5%.

Workup

customAfter completion of the reaction
customthe reaction mixture was quenched with 5% aqueous hydrochloric acid
customBoth organic and aqueous layers were separated
extractionthe aqueous layers were extracted with ethyl acetate
washwashed with water
distillationdistilled off the solvent

Sources & evidence

ORD record: ord-304723e87d1f4697b9faa19728eea442
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102664B2

Reaction notes

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