N-methyl-2-pyrrolidone → Methyl 6-cyano-7-fluorochroman-4-carboxylate

HRID 1626382Notes

Reaction equation

HRID 1626382 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[O:8][CH2:7][CH2:6][CH:5]2[C:13]([O:15][CH3:16])=[O:14].[CH3:17][N:18]1CCCC1=O>>[C:17]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[O:8][CH2:7][CH2:6][CH:5]2[C:13]([O:15][CH3:16])=[O:14])#[N:18]

Participants

3

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 46929189Methyl 6-bromo-7-fluoro-chromane-4-carboxylate

Product 1

HCID 67080208Methyl 6-cyano-7-fluorochroman-4-carboxylateYield 77%

Conditions

Temperature
160 °C

Procedure

Methyl 6-bromo-7-fluoro-3,4-dihydro-2H-chromene-4-carboxylate (415 mg, 1.44 mmol) was diluted with N-methylpyrrolidone (5 mL) followed by the addition of Cu(I)CN (643 mg, 7.18 mmol). The reaction was bubbled with argon for 20 minutes, then heated at 160° C. under a slight argon bubble for 6 hours. The reaction was cooled to ambient temperature and loaded directly onto a Biotage 25 column (silica gel), eluting with 5% ethyl acetate/hexanes to 100% ethyl acetate to yield the title compound (260 mg, 77.0% yield).

Workup

  1. customThe reaction was bubbled with argon for 20 minutes
  2. custombubble for 6 hours
  3. temperatureThe reaction was cooled to ambient temperature
  4. washeluting with 5% ethyl acetate/hexanes to 100% ethyl acetate

Sources & evidence

ORD record
ord-8c1d8416522d4abdb037d7e2185a0cb4
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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