Hydrochloric Acid → 1-(2-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

HRID 928523ノート

反応式

HRID 928523 の反応式
[CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.C(OCN1C2N=CN=C(C3C=NN([CH:37]([O:39][CH2:40][CH3:41])[CH3:38])C=3)C=2C=C1)(=O)C(C)(C)C.Cl.C([O-])(O)=O.[Na+]>O1CCOCC1.C1(C)C=CC=CC=1>[CH2:37]([O:39][CH2:40][CH2:41][N:12]1[CH:13]=[C:9]([B:4]2[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]2)[CH:10]=[N:11]1)[CH3:38]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57868870(4-(1-(1-Ethoxyethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

生成物 1

HCID 684741121-(2-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole収率 97.3%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
37.5 °C

実験手順

A 22 L 4-neck flask equipped with a mechanical stirrer, thermowell, addition funnel, condenser and N2 inlet was charged with 4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (17, 1.42 kg, 7.32 mol), toluene (9.5 L) and ethyl vinyl ether (18, 790.5 g, 1050 mL, 10.98 mol, 1.50 equiv). A 4 M HCl in dioxane (50 mL) was added via an addition funnel over 10 minutes and the resulting reaction mixture was heated at 35-40° C. for 7 hr to give a clear homogeneous solution. When the reaction was shown to be complete by GC, solid NaHCO3 (130 g) was added and the mixture was stirred for 1 hr before being filtered. The filtrate was concentrated under reduced pressure. Heptane (200 mL) was added to the residue to affect crystallization. The solid was collected by filtration and dried in a vacuum oven to afford 1-(ethoxyethyl)-4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (19, 1.896 Kg, 1.948 Kg theoretical, 97.3%) as a white to off-white solid. For 19: 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.09 (s, 1H), 8.58 (s, 1H), 7.62 (s, 1H), 5.55 (q, 1H, J=6.1 Hz), 3.37 (dq, 1H, J=7.1, 9.6 Hz), 3.12 (dq, 1H, J=7.0, 9.7 Hz), 1.56 (d, 3H, J=6.0 Hz), 1.24 (s, 12H), 1.00 (t, 3H, J=7.0 Hz); C13H23BN2O3 (MW, 266.14), LCMS (EI) m/e 267 (M++H).

後処理

  1. customA 22 L 4-neck flask equipped with a mechanical stirrer
  2. additionthermowell, addition funnel, condenser and N2 inlet
  3. customthe resulting reaction mixture
  4. customto give a clear homogeneous solution
  5. additionwas added
  6. filtrationbefore being filtered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. additionHeptane (200 mL) was added to the residue
  9. customcrystallization
  10. filtrationThe solid was collected by filtration
  11. customdried in a vacuum oven

出典と根拠

ORDレコード
ord-731b247989d9446bb431b2f434ce32c5
出典データセット
uspto-grants-2016_03
特許番号
US09290506B2

反応ノート

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