Tetrahydrofuran → (4-chlorophenyl)(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-3-yl)methanol

HRID 2401724ノート

反応式

HRID 2401724 の反応式
Br[C:2]1[S:6][C:5]([C:7]2[N:11]=[CH:10][N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:8]=2)=[C:4]([CH:18]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)[OH:19])[CH:3]=1.O1CCCC1.C([Mg]Cl)(C)C.C(O[B:41]1[O:45][C:44]([CH3:47])([CH3:46])[C:43]([CH3:49])([CH3:48])[O:42]1)(C)C>>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([CH:18]([C:4]2[CH:3]=[C:2]([B:41]3[O:45][C:44]([CH3:47])([CH3:46])[C:43]([CH3:49])([CH3:48])[O:42]3)[S:6][C:5]=2[C:7]2[N:11]=[CH:10][N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:8]=2)[OH:19])=[CH:21][CH:22]=1

参加物

5

反応物 4

HCID 8028TetrahydrofuranHCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 66749509(5-bromo-2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)thiophen-3-yl)(4-chlorophenyl)methanolHCID 178418918HCID 178418918、化合物

生成物 1

HCID 66749137(4-chlorophenyl)(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-3-yl)methanol収率 93%

実験手順

To a mixture of {5-bromo-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-3-thienyl}(4-chlorophenyl)methanol (5.19 g, 11.4 mmol) in tetrahydrofuran (146.9 mL, 1811 mmol) was added isopropylmagnesium chloride (1M in THF, 34.2 mL, 34.2 mmol) at −40° C. under argon. After addition, the reaction temperature was raised to rt for 15 min. The mixture was then cooled to −78° C. and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (8.149 mL, 39.94 mmol) was added. After the addition, the mixture was brought to rt. After 1 h, the mixture was heated at 75° C. overnight. The mixture was cooled to rt and quenched with saturated ammonium chloride solution. The mixture was stirred for 10 min then extracted with EtOAc. The organic layer was dried and evaporated in vacuum. The mixture was purified by chromatography to afford (4-chlorophenyl)(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-3-yl)methanol as a thick oil (5.32 g, 65.0%). LCMS: (FA) ES+ 502.2, 504.1.

後処理

  1. additionAfter addition
  2. temperatureThe mixture was then cooled to −78° C.
  3. additionAfter the addition
  4. customwas brought to rt
  5. temperaturethe mixture was heated at 75° C. overnight
  6. temperatureThe mixture was cooled to rt
  7. customquenched with saturated ammonium chloride solution
  8. extractionthen extracted with EtOAc
  9. customThe organic layer was dried
  10. customevaporated in vacuum
  11. customThe mixture was purified by chromatography

出典と根拠

ORDレコード
ord-311f4248766e471dba8f02a4a898b171
出典データセット
uspto-grants-2014_08
特許番号
US08796268B2

反応ノート

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