Dimethylformamide → 4-(Hydroxymethyl)thiophene-2-carbonitrile

HRID 2748

Reaction equation

I[C:2]1[S:6][CH:5]=[C:4]([CH2:7][OH:8])[CH:3]=1.[CH3:9][N:10](C=O)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N>[OH:8][CH2:7][C:4]1[CH:3]=[C:2]([C:9]#[N:10])[S:6][CH:5]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (5-iodo-thiophene-3-yl)methanol (42 g, 176 mmol) in 150 mL of DMF is added zinc cyanide (12.4 g, 106 mmol) and tetrakis(triphenylphospine)palladium (0) (8.13 g, 7.04 mmol). The solution is heated to 80° C. After 6 h, the solution is diluted with 3 L of EtOAc. The resulting solution is washed with 1N NH4OH, H2O and sat. NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with gradient of 20% EtOAc/hexanes to 30% EtOAc/hexanes to afford the title compound (10 g, 72 mmol) as a clear oil.

Workup

washThe resulting solution is washed with 1N NH4OH, H2O and sat. NaCl
dry with materialThe organic layer is dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude product is purified by column chromatography
washeluting with gradient of 20% EtOAc/hexanes to 30% EtOAc/hexanes

Sources & evidence

ORD record: ord-e6dea7c2aa4947e5bcc870d26f4d2244
Source dataset: uspto-grants-1998_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05731315

Linked notes

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