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

HRID 855011노트

반응식

HRID 855011 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
80 °C

실험 절차

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

후처리

  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

출처 및 근거

ORD 기록
ord-d1eddef5fd54453eb69146c789b60163
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07259266B2

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