Sodium Bicarbonate → 4-{4-[(1-isopropylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-carboxamide

HRID 272946ノート

反応式

HRID 272946 の反応式
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3([C:23]#[N:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C([O-])(O)=[O:26].[Na+]>>[NH3:4].[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3([C:23]([NH2:24])=[O:26])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[CH:13][CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

参加物

4

反応物 2

HCID 516892Sodium BicarbonateHCID 115008424-[4-(1-Isopropylpiperidin-4-yloxy)phenyl]tetrahydropyran-4-carbonitrile

生成物 2

HCID 222AmmoniaHCID 115447584-{4-[(1-isopropylpiperidin-4-yl)oxy]phenyl}tetrahydro-2H-pyran-4-carboxamide収率 42%

実験手順

4-[4-(1-Isopropylpiperidin-4-yloxy)phenyl]tetrahydropyran-4-carbonitrile (50 mg, 0.152 mmol) was combined with boron trifluoride-acetic acid complex (500 μL, 3.6 mmol) and stirred at ambient temperature for 18 hours, followed by 65° C. for 3 hours. The reaction mixture was allowed to cool and then basified with saturated NaHCO3 solution (15 mL). The product was extracted with dichloromethane (2×35 mL). The combined organic extracts were dried using Na2SO4 filtered and concentrated in vacuo. The compound was purified by column chromatography on silica gel (15 g), eluting with dichloromethane:methanol:ammonia, (96:4:0.4) to dichloromethane:methanol:ammonia, (90:10:1) to give the title compound as a white solid (22 mg, 42%). 1H NMR (400 MHz, CD3OD) δ7.3 (d, 2H), 6.9 (d, 2H), 4.4 (m, 1H), 3.8 (m, 2H), 3.65 (m, 2H), 2.78-2.85 (m, 3H), 2.5 (m, 2H), 2.4 (d, 2H), 1.95-2.08 (m, 4H), 1.8 (m, 2H), 1.1 (d, 6H)

後処理

  1. waitfollowed by 65° C. for 3 hours
  2. temperatureto cool
  3. extractionThe product was extracted with dichloromethane (2×35 mL)
  4. customThe combined organic extracts were dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe compound was purified by column chromatography on silica gel (15 g)
  8. washeluting with dichloromethane

出典と根拠

ORDレコード
ord-ff6d9642cb51472f9295861e223ea9c4
出典データセット
uspto-grants-2008_11
特許番号
US07456164B2

反応ノート

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