Potassium Carbonate → tert-Butyl 7-(4-carbamoylphenoxy)-6-cyanochroman-4-carboxylate

HRID 1626388Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1F)[O:9][CH2:8][CH2:7][CH:6]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])#[N:2].[OH:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([NH2:28])=[O:27])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1.C(OCC)(=O)C>[C:26]([C:25]1[CH:29]=[CH:30][C:22]([O:21][C:12]2[CH:11]=[C:10]3[C:5]([CH:6]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7][CH2:8][O:9]3)=[CH:4][C:3]=2[C:1]#[N:2])=[CH:23][CH:24]=1)(=[O:27])[NH2:28]

Participants

Conditions

Temperature: 120 °C

Procedure

tert-butyl 6-cyano-7-fluorochroman-4-carboxylate (290 mg, 1.05 mmol), 4-hydroxybenzamide (172 mg, 1.25 mmol) and potassium carbonate (347 mg, 2.51 mmol) were diluted with dry NMP (4 mL). The reaction was bubbled with argon for 10 minutes and then heated at 120° C. for 12 hours under a slight argon bubble. The reaction was cooled and loaded directly onto a biotage 40 M cartridge, eluting with 20% ethyl acetate/hexanes to 100% ethyl acetate to yield 1 g of the crude product which was found to contain NMP. The residue was taken up in ethyl acetate and washed twice with water and then brine. The organic layer was dried over magnesium sulfate, filtered and concentrated to provide the desired product (343 mg, 83.2% yield) as a white foam.

Workup

customThe reaction was bubbled with argon for 10 minutes
custombubble
temperatureThe reaction was cooled
washeluting with 20% ethyl acetate/hexanes to 100% ethyl acetate
customto yield 1 g of the crude product which
washwashed twice with water
dry with materialThe organic layer was dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-7e69ab0e696b4935b8d04bf867f93f50
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785445B2

Reaction notes

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