Ethanol → 6-chloro-7-(4-ethynyl-2-methylphenoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

HRID 855011Notes

Reaction equation

HRID 855011 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]#[CH:20])=[CH:15][C:14]=1[CH3:21])[O:8][CH:7]([C:22]([F:25])([F:24])[F:23])[C:6]([C:26]([O:28]CC)=[O:27])=[CH:5]2.[OH-].[Li+].C(O)C>O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]#[CH:20])=[CH:15][C:14]=1[CH3:21])[O:8][CH:7]([C:22]([F:25])([F:23])[F:24])[C:6]([C:26]([OH:28])=[O:27])=[CH:5]2

Participants

6

Reactant 3

HCID 702EthanolHCID 3939Lithium HydroxideHCID 86599479ethyl 6-chloro-7-(4-ethynyl-2-methylphenoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 114071826-chloro-7-(4-ethynyl-2-methylphenoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acidYield 32.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

The product of step 1 (230 mg, 0.53 mmol) was dissolved in 3 ml of tetrahydrofuran. To the resulting solution was added a solution of lithium hydroxide (111 mg, 2.6 mmol) in 3 mL of water, followed by addition of 3 mL of ethanol. The resulting solution was heated to 80° C. for one hr, LC-MS indicated that the reaction was complete. The volatiles were removed. The residue was diluted with water, and acidified at 0° C. with dilute hydrochloric acid to pH=1.0. The product was extracted with ethyl acetate, and dried over anhydrous magnesium sulfate. After removing the volatiles, the crude product was purified by reverse phase HPLC. The product was obtained 70 mg (28.8%) of a light yellow solid: 1H NMR (CDCl3/300 MHz) 7.82 (s, 1H), 7.48(s, 1H), 7.42-7.40(m, 2H), 6.93(d, J=8.1 Hz, 1H), 6.36(s, 1H), 5.66(q, J=6.9 Hz, 1H), 3.11(s, 1H), 2.23(s, 3H). MS (ESI+) 409.0(M+1, 100). MS(ES−) 407.0(M−H, 100). HRMS (ES−) m/z calcd for (M−H; C20H11ClF3O4): 407.0292, found: 407.0317

Workup

  1. customThe volatiles were removed
  2. additionThe residue was diluted with water
  3. customacidified at 0° C. with dilute hydrochloric acid to pH=1.0
  4. extractionThe product was extracted with ethyl acetate
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customAfter removing the volatiles
  7. customthe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-d1eddef5fd54453eb69146c789b60163
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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