Perchloric Acid → (S)-methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 574355

反応式

HRID 574355 の反応式
[Br:1][C:2]1[CH:25]=[C:5]2[N:6]=[C:7]([CH3:24])[C:8]([C@H:18]([OH:23])[C:19]([O:21][CH3:22])=[O:20])=[C:9]([N:10]3[CH2:15][CH2:14][C:13]([CH3:17])([CH3:16])[CH2:12][CH2:11]3)[N:4]2[N:3]=1.Cl(O)(=O)(=O)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl.C(OC(C)(C)C)(=O)C>[Br:1][C:2]1[CH:25]=[C:5]2[N:6]=[C:7]([CH3:24])[C:8]([C@H:18]([O:23][C:8]([CH3:18])([CH3:9])[CH3:7])[C:19]([O:21][CH3:22])=[O:20])=[C:9]([N:10]3[CH2:15][CH2:14][C:13]([CH3:17])([CH3:16])[CH2:12][CH2:11]3)[N:4]2[N:3]=1

参加物

6

反応物 3

HCID 24247Perchloric AcidHCID 516892Sodium BicarbonateHCID 86695080(S)-methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

生成物 1

HCID 86695081(S)-methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate収率 86.8%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 10908tert-Butyl acetate溶媒

実験手順

To a solution of (S)-methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (5.68 g, 13.81 mmol, 1 equiv) in DCM (92 mL) and t-butyl acetate (184 mL) was added 70% perchloric acid (3.3 mL, 55.2 mmol, 4 equiv). The reaction turned pale yellow. After 3 h, the reaction was added very cautiously to a saturated aqueous solution of NaHCO3 and extracted with CHCl3 (×3). Combined organic extracts dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel flash chromatography (0-70% EtOAc/hexane) to provide (S)-methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate as a pale yellow solid (2.8 g, 43%) and recovered starting material (3.0 g, 53%). 1H NMR (400 MHz, CDCl3) δ 6.54 (s, 1H), 5.92 (s, 1H), 3.74 (s, 3H), 2.59 (s, 3H), 1.58 (s, 8H), 1.24 (s, 9H), 1.11 (s, 6H); LCMS (ESI, M+1):467.3.

後処理

  1. extractionextracted with CHCl3 (×3)
  2. dry with materialCombined organic extracts dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by silica gel flash chromatography (0-70% EtOAc/hexane)

出典と根拠

ORDレコード
ord-f868f1ab2ec345dab43f8a5c615abaca
出典データセット
uspto-grants-2015_05
特許番号
US09034882B2

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