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Hydrochloric Acid → 2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylic acid

HRID 403361
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HRID 403361 반응식
C([O:3][C:4]([C:6]1[N:7]=[C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17](=[O:29])[CH2:18][N:19]3[C:23]([CH3:24])=[CH:22][C:21]([C:25]([F:28])([F:27])[F:26])=[N:20]3)[CH2:13][CH2:12]2)[S:9][CH:10]=1)=[O:5])C.[OH-].[Na+].Cl>C1COCC1>[CH3:24][C:23]1[N:19]([CH2:18][C:17]([N:14]2[CH2:15][CH2:16][CH:11]([C:8]3[S:9][CH:10]=[C:6]([C:4]([OH:5])=[O:3])[N:7]=3)[CH2:12][CH2:13]2)=[O:29])[N:20]=[C:21]([C:25]([F:28])([F:26])[F:27])[CH:22]=1
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참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66911511ethyl-2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylate

생성물 1

HCID 666014572-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarboxylic acid수율 94%

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매

실험 절차

To a solution of 2-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazole-4-carboxylic acid ethyl ester (2.67 g, 6.2 mmol) in THF (20 mL) is added aqueous solution of sodium hydroxide (2 M, 4.65 mL, 9.3 mmol) at RT. After stirring 3 h at RT, the reaction mixture is acidified with 2M aqueous solution of HCl until pH 2-3, and the solution is extracted with ethylacetate (20 mL). The aqueous layer is re-extracted with ethylacetate (20 mL) and the combined organic layers are washed with brine (10 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure to give 2-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazole-4-carboxylic acid (2.33 g, 94%), which can be used in the next step without further purification. 1H-NMR (400 MHz, d6-acetone): δ=1.69-1.82 (m, 1H), 1.87-2.02 (m, 1H), 2.16-2.37 (m, 2H), 2.38 (s, 3H), 2.89-2.99 (m, 1H), 3.38-3.48 (m, 2H), 4.14-4.22 (m, 1H), 4.50-4.69 (m, 1H), 5.20-5.36 (2 d, 2H (diastereotopic)), 6.41, (s, 1H), 8.34 (s, 1H). MS: m/z=403 (M+1).

후처리

  1. extractionthe solution is extracted with ethylacetate (20 mL)
  2. extractionThe aqueous layer is re-extracted with ethylacetate (20 mL)
  3. washthe combined organic layers are washed with brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure

출처 및 근거

ORD 기록
ord-adaa526f1ec64b75a2d003b9b6aab69a
출처 데이터셋
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08748431B2

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