Bromoacetonitrile → Ethyl 1-(Cyanomethyl)-6,6-difluoro-4,5,6,7-tetrahydro-1H-indole-2-carboxylate

HRID 519329Notes

Reaction equation

[F:1][C:2]1([F:16])[CH2:10][C:9]2[NH:8][C:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:6][C:5]=2[CH2:4][CH2:3]1.[H-].[Na+].Br[CH2:20][C:21]#[N:22]>CN(C)C=O.O>[C:21]([CH2:20][N:8]1[C:9]2[CH2:10][C:2]([F:1])([F:16])[CH2:3][CH2:4][C:5]=2[CH:6]=[C:7]1[C:11]([O:13][CH2:14][CH3:15])=[O:12])#[N:22]

Participants

Conditions

Temperature: 20 °C

Procedure

Into a 250-mL 3-necked round-bottom flask was placed a solution of 113l (5.0 g, 21.81 mmol, 1.00 equiv) in N,N-dimethylformamide (50 mL), followed by the addition of sodium hydride (1.3 g, 54.17 mmol, 1.40 equiv, 60%) in several batches at 0° C. over 10 min. (FIG. 14). To this was added 2-bromoacetonitrile (3.7 g, 30.85 mmol, 1.40 equiv) dropwise with stirring at 20° C. over 10 min. The resulting solution was stirred at room temperature for 7 h, diluted with 100 mL of water and extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with 1×100 mL of water and 1×100 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluting with ethyl acetate/petroleum ether (1:20) to afford 3.3 g (56%) of 113m as a light yellow oil.

Workup

customInto a 250-mL 3-necked round-bottom flask was placed
stirringThe resulting solution was stirred at room temperature for 7 h
extractionextracted with 3×50 mL of ethyl acetate
washThe combined organic layers were washed with 1×100 mL of water and 1×100 mL of brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under vacuum
customThe residue was purified on a silica gel column
washeluting with ethyl acetate/petroleum ether (1:20)

Sources & evidence

ORD record: ord-bb14b3d36c654a2a895faaf6dc78dbdd
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115152B2

Reaction notes

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