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 2401724노트

반응식

HRID 2401724 반응식
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

참가 물질

5

반응물 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, 화합물

생성물 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)methanol수율 93%

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-311f4248766e471dba8f02a4a898b171
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08796268B2

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