Potassium Carbonate → Methyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6-cyanochroman-4-carboxylate

HRID 510607Notes

Reaction equation

HRID 510607 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1F)[O:9][C:8](C)(C)[CH2:7][CH:6]2[C:16]([O:18][CH3:19])=[O:17])#[N:2].[OH:20][C:21]1[CH:33]=[CH:32][C:24]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CN1CCCC1=O>[C:28]([O:27][C:25]([C:24]1[CH:23]=[CH:22][C:21]([O:20][C:12]2[CH:11]=[C:10]3[C:5]([CH:6]([C:16]([O:18][CH3:19])=[O:17])[CH2:7][CH2:8][O:9]3)=[CH:4][C:3]=2[C:1]#[N:2])=[CH:33][CH:32]=1)=[O:26])([CH3:31])([CH3:29])[CH3:30]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 117640tert-Butyl 4-hydroxybenzoateHCID 67080271Methyl 6-cyano-7-fluoro-2,2-dimethylchroman-4-carboxylate

Product 1

HCID 67080240Methyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6-cyanochroman-4-carboxylateYield 32.8%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

Methyl 6-cyano-7-fluorochroman-4-carboxylate (from Example 3, Step E) (700 mg, 2.98 mmol), tert-butyl 4-hydroxybenzoate (578 mg, 2.98 mmol) and K2CO3 (494 mg, 3.57 mmol) were diluted with N-methylpyrrolidone (6 mL) and bubbled with argon for 10 minutes. The reaction was heated to 110° C. and stirred for 5 hours. The reaction was loaded directly onto a Biotage 40M cartridge and eluted with 5% ethyl acetate/hexanes to 100% ethyl acetate to yield the title compound (400 mg, 32.8% yield).

Workup

  1. custombubbled with argon for 10 minutes
  2. washeluted with 5% ethyl acetate/hexanes to 100% ethyl acetate

Sources & evidence

ORD record
ord-5b6590931aba4160bda19c85b9b2e952
Source dataset
uspto-grants-2015_08
Patent number
US09096567B2

Reaction notes

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