Hydrochloric Acid → 4-(6-Cyano-4-(methoxycarbonyl)chroman-7-yloxy)-3-methylbenzoic acid

HRID 1048116Notes

Reaction equation

C([O-])([O-])=O.[K+].[K+].[C:7]([C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1F)[O:15][CH2:14][CH2:13][CH:12]2[C:20]([O:22][CH3:23])=[O:21])#[N:8].[OH:24][C:25]1[CH:37]=[CH:36][C:28]([C:29]([O:31]C(C)(C)C)=[O:30])=[CH:27][C:26]=1[CH3:38].Cl>CN1C(=O)CCC1>[C:7]([C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:24][C:25]1[CH:37]=[CH:36][C:28]([C:29]([OH:31])=[O:30])=[CH:27][C:26]=1[CH3:38])[O:15][CH2:14][CH2:13][CH:12]2[C:20]([O:22][CH3:23])=[O:21])#[N:8]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of K2CO3 (0.026 g, 0.19 mmol), methyl 6-cyano-7-fluoro-3,4-dihydro-2H-chromene-4-carboxylate (0.040 g, 0.17 mmol), and tert-butyl 4-hydroxy-3-methylbenzoate (0.039 g, 0.19 mmol) in 0.5 ml NMP was heated under argon at 120° C. for 24 hours. The reaction was cooled, poured into 10% aqueous HCl, and extracted with ethyl acetate. The organic extracts were dried with sodium sulfate and purified on silica gel. Elution with 25% ethyl acetate-hexanes provided material that still contained impurities. The mixture was deprotetcted with to 1:1 trifluoracetic acid-dichloromethane to provide the title compound (13 mg, still impure) which was used directly in the next step.

Workup

temperatureThe reaction was cooled
extractionextracted with ethyl acetate
dry with materialThe organic extracts were dried with sodium sulfate
custompurified on silica gel
washElution with 25% ethyl acetate-hexanes provided material that still contained impurities

Sources & evidence

ORD record: ord-97ee1d2748b6487cac15e67c8dea39b8
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569522B2

Reaction notes

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