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

HRID 855011Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 855011
[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

Komponenten

6

Edukt 3

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

Produkt 1

HCID 114071826-chloro-7-(4-ethynyl-2-methylphenoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acidAusbeute 32,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-d1eddef5fd54453eb69146c789b60163
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07259266B2

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