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

HRID 561194ノート

反応式

HRID 561194 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-1a94afc4679d47968befad5db89bef54
出典データセット
uspto-grants-2011_11
特許番号
US08063224B2

反応ノート

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