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

HRID 272946Notes

Reaction equation

HRID 272946 reaction equation
[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]

Participants

4

Reactant 2

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

Product 2

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

Procedure

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)

Workup

  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

Sources & evidence

ORD record
ord-ff6d9642cb51472f9295861e223ea9c4
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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