N-methyl-2-pyrrolidone → Methyl 6-cyano-7-fluoro-2,2-dimethylchroman-4-carboxylate

HRID 1047996Notes

Reaction equation

HRID 1047996 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[O:8][C:7]([CH3:14])([CH3:13])[CH2:6][CH:5]2[C:15]([O:17][CH3:18])=[O:16].[CH3:19][N:20]1CCCC1=O>>[C:19]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[O:8][C:7]([CH3:14])([CH3:13])[CH2:6][CH:5]2[C:15]([O:17][CH3:18])=[O:16])#[N:20]

Participants

3

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 67080243methyl 6-bromo-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromene-4-carboxylate

Product 1

HCID 67080271Methyl 6-cyano-7-fluoro-2,2-dimethylchroman-4-carboxylateYield 62.3%

Conditions

Temperature
160 °C

Procedure

methyl 6-bromo-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromene-4-carboxylate (232 mg, 0.732 mmol) was diluted with N-methylpyrrolidone (4 mL) followed by the addition of Cu(I)CN (328 mg, 3.66 mmol). The reaction was bubbled with Argon for 15 minutes and then heated at 160° C. The reaction was stirred for 5 hours and then allowed to cool. The reaction was loaded directly onto a Biotage 25 column eluting with 5% ethyl acetate/hexanes to 100% ethyl acetate to yield the title compound (120 mg, 62.3% yield).

Workup

  1. customThe reaction was bubbled with Argon for 15 minutes
  2. temperatureto cool
  3. washeluting with 5% ethyl acetate/hexanes to 100% ethyl acetate

Sources & evidence

ORD record
ord-307bf265af4d4ffeaa419b816b5c7ccb
Source dataset
uspto-grants-2013_10
Patent number
US08569522B2

Reaction notes

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