Sodium Iodide → 2-Cyanomethyl-5-(5'-fluoro-2-methoxyphenethyl)tetrahydrofuran

HRID 1919537Notes

Reaction equation

Br[CH2:2][CH:3]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])[O:4]1.[Na+].[I-].[C-:21]#[N:22].[K+].[Na].C([O-])(O)=O.[Na+].O>CS(C)=O>[C:21]([CH2:2][CH:3]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])[O:4]1)#[N:22]

Participants

Conditions

Temperature: 70 °C

Procedure

To a vial under an atmosphere of Ar(g) was added 10 (1.23 g, 4.3 mmol), NaI (100 mg), potassium cyanide (0.7 g, 10.6 mmol), and dry DMSO (15 mL). The mixture obtained was heated to 70° C. under an atmosphere of Ar for 12 h. After cooling to room temperature, the reaction mixture was poured into a separatory funnel containing sodium bicarcarbonate aqueous solution (sat. NaHCO3/H2O, 50:50, v:v, 80 mL). The organic fraction was extracted with EtOAc (3×60 mL) and the combined organic layers were washed with brine (50 mL) and dried over sodium sulfate. The solvent was then removed in vacuo and the crude product obtained (0.45 g, 86%) was purified by flash column chromatography (EtOAc/hexane, 10:90, v:v, Rf=0.11); as a 2:1 mixture of trans/cis diastereomers. 1H NMR (500 MHz, CDCl3) δ 6.88-6.82 (m, 2 H), 6.74 (dd, J=4.3, 8.5 Hz, 1 H), 4.26 (m, 1 H), 4.09 (m, 0.65 H), 3.90 (m, 0.35 H) 3.79 (s, 3 H), 2.72-2.53 (m, 4 H), 2.22-2.04 (m, 2 H), 1.84-1.6 (m, 4 H).

Workup

customThe mixture obtained
temperatureAfter cooling to room temperature
additionthe reaction mixture was poured into a separatory funnel
extractionThe organic fraction was extracted with EtOAc (3×60 mL)
washthe combined organic layers were washed with brine (50 mL)
dry with materialdried over sodium sulfate
customThe solvent was then removed in vacuo

Sources & evidence

ORD record: ord-be0924d05166426da38f6bd3d3bbf64a
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08168635B2

Reaction notes

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