Hydrochloric Acid → ethyl [5-(5-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3,4-thiadiazol-2-yl)-2H-tetrazol-2-yl]acetate

HRID 561194노트

반응식

HRID 561194 반응식
[N:1]1[NH:2][N:3]=[N:4][C:5]=1[C:6]1[S:10][C:9]([N:11]2[CH2:16][CH2:15][CH:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:26])[F:25])[CH2:13][CH2:12]2)=[N:8][N:7]=1.[H-].[Na+].Br[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33].Cl>CN(C=O)C>[F:25][C:24]([F:27])([F:26])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[O:17][CH:14]1[CH2:13][CH2:12][N:11]([C:9]2[S:10][C:6]([C:5]3[N:1]=[N:2][N:3]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[N:4]=3)=[N:7][N:8]=2)[CH2:16][CH2:15]1

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 159806391-[5-(2H-Tetrazol-5-yl)-1,3,4-thiadiazol-2-yl}-4-[2-(trifluoromethyl)phenoxy]piperidine

생성물 1

HCID 86620455ethyl [5-(5-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3,4-thiadiazol-2-yl)-2H-tetrazol-2-yl]acetate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

A solution of 1-[5-(2H-tetrazol-5-yl)-1,3,4-thiadiazol-2-yl]-4-[2-(trifluoromethyl)phenoxy]piperidine (262 mg, 0.66 mmol) in DMF (5 mL) was treated with NaH (60% in oil) (42 mg, 1.05 mmol) at −78° C. The mixture was warmed to 0° C. and, after 10 min, ethyl bromoacetate (150 μL, 1.35 mmol) was added dropwise. The final reaction mixture was warmed and stirred at room temperature until TLC indicated disappearance of the starting material. The reaction mixture was poured into aqueous 1 N HCl, extracted with EtOAc and washed with brine. The organic layer was dried (Na2SO4) and filtered. Solvents were removed in vacuo to afford the crude product, which was purified by column chromatography on silica gel (eluting with 10-50% EtOAc/hexanes) to afford ethyl [5-(5-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3,4-thiadiazol-2-yl)-2H-tetrazol-2-yl]acetate as the more polar regioisomer, Rf=0.2 (50% EtOAc/hexanes). 1H NMR (400 MHz, acetone-d6): δ7.70-7.61 (m, 2H), 7.40 (d, 1H), 7.14 (t, 1H), 5.81 (s, 2H), 5.10-5.04 (m, 1H), 4.31 (q, 2H), 3.94-3.85 (m, 2H), 3.86-3.77 (m, 2H), 2.29-2.20 (m, 2H), 2.11-2.03 (dd, 2H), 1.31 (t, 3H).

후처리

  1. customThe final reaction mixture
  2. temperaturewas warmed
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customSolvents were removed in vacuo
  8. customto afford the crude product, which
  9. customwas purified by column chromatography on silica gel (eluting with 10-50% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-1a94afc4679d47968befad5db89bef54
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063224B2

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