Lithium hydroxide, monohydrate → 8-iodo-7-methoxy-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

HRID 855024Notes

Reaction equation

HRID 855024 reaction equation
[I:1][C:2]1[C:3]([O:21][CH3:22])=[CH:4][CH:5]=[C:6]2[C:11]=1[O:10][CH:9]([C:12]([F:15])([F:14])[F:13])[C:8]([C:16]([O:18]CC)=[O:17])=[CH:7]2.O.[OH-].[Li+]>O1CCCC1.O>[I:1][C:2]1[C:3]([O:21][CH3:22])=[CH:4][CH:5]=[C:6]2[C:11]=1[O:10][CH:9]([C:12]([F:15])([F:14])[F:13])[C:8]([C:16]([OH:18])=[O:17])=[CH:7]2

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 58934894ethyl 8-iodo-7-methoxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 589344428-iodo-7-methoxy-2-(trifluoromethyl)-2H-chromene-3-carboxylic acidYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the solution of 0.4 g (0.93 mmol) of ethyl 8-iodo-7-methoxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate in 8 mL of tetrahydrofuran was added a solution of 155 mg (3.7 mmol) of lithium hydroxide hydrate (LiOH—H2O) in 15 mL of water. The resulting solution was heated to reflux for one h. After cooling to room temperature, the volatiles were removed, the residue was acidified at 0° C. to pH=1.5 with dilute hydrochloric acid. The product was extracted with ethyl ether. The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and concd in vacuo to afford 0.30 g (81%) of a light yellow solid: 1H NMR (CDCl3/400 MHz) 7.67(s, 1H), 7.18(d, J=8.4 Hz, 1H), 6.51(d, J=8.4 Hz, 1H), 5.78(q, J=6.8 Hz, 1H), 3.92(s, 3H). MS (ESI+) 400.9 (M+1, 100). MS(ES−) 398.9(M−H, 100). HRMS (ES−) m/z calcd for (M−H; C12H7F3O4): 398.9336, found 398.9368.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux for one h
  3. customthe volatiles were removed
  4. customwas acidified at 0° C. to pH=1.5 with dilute hydrochloric acid
  5. extractionThe product was extracted with ethyl ether
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate and concd in vacuo

Sources & evidence

ORD record
ord-b5a7d543e97842baa59caa545ab1d23b
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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