Ethanol → 6-[(1E)-3-amino-3-oxoprop-1-enyl]-8-chloro-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

HRID 854994Notes

Reaction equation

[NH2:1][C:2](=[O:25])/[CH:3]=[CH:4]/[C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([Cl:15])[CH:14]=1)[O:11][CH:10]([C:16]([F:19])([F:18])[F:17])[C:9]([C:20]([O:22]CC)=[O:21])=[CH:8]2.O.[OH-].[Li+].C(O)C>C1COCC1.O>[NH2:1][C:2](=[O:25])/[CH:3]=[CH:4]/[C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([Cl:15])[CH:14]=1)[O:11][CH:10]([C:16]([F:17])([F:18])[F:19])[C:9]([C:20]([OH:22])=[O:21])=[CH:8]2

Participants

Conditions

Temperature: 80 °C

Procedure

The product of step 1 was dissolved in 3 mL of THF and treated with a solution of 0.13 g (2.55 mmol) lithium hydroxide hydrate in 3 mL of water. The mixture was treated with 3 mL of ethanol and heated to 80° C. for two hrs. The volatiles were removed, the residue was acidified at 0° C. to pH=1.0 with dilute hydrochloric acid. The product was extracted with ethyl acetate, washed with brine and dried over anhydrous magnesium sulfate. Concentration of the organic fraction afforded 0.169 g (48.6%) of an off-white solid: 1H NMR(DMSO/300 MHz) 7.87(s, 1H), 7.70(d, J=2.1 HZ, 1H), 7.55(d, J=2.1 Hz, 1H), 7.48(d, J=15.9 Hz, 1H), 6.63(d, J=15.9, 1H), 5.96(q, J=6.6 Hz, 1H). MS (ESI+) 348.0 (M+1, 100). MS(ES−) 346.0(M−1, 100). HRMS (ES−) m/z calcd for (M−H; C14H8ClF3NO4): 346.0088, found 346.0078.

Workup

customThe volatiles were removed
customwas acidified at 0° C. to pH=1.0 with dilute hydrochloric acid
extractionThe product was extracted with ethyl acetate
washwashed with brine
dry with materialdried over anhydrous magnesium sulfate

Sources & evidence

ORD record: ord-3634b7093a3e43da83ba5a72b32dc4de
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07259266B2

Reaction notes

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