Water → HCID 58495602, compound

HRID 1190979Notes

Reaction equation

HRID 1190979 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([O:8][CH:9]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[Cu][C:17]#[N:18].CN1C(=O)CCC1.O>C(OCC)C>[CH:9]1([O:8][C:5]2[CH:4]=[CH:3][C:2]([C:17]#[N:18])=[N:7][CH:6]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1

Participants

6

Reactant 4

HCID 962WaterHCID 13387N-methyl-2-pyrrolidoneHCID 58495535HCID 58495535, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 58495602HCID 58495602, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
190 °C

Procedure

Add 6-chloro-3-cycloheptyloxy-pyridine (2.35 g, 10.4 mmol) and copper(I) cyanide (1.16 g, 13.1 mmol) to NMP (25 mL). Heat the mixture to 190° C. and stir overnight. Cool the mixture to room temperature, add water (50 mL) and diethyl ether (30 mL). Extract the aqueous phase with diethyl ether (3×25 mL). Wash the combined organic extracts with brine (20 mL), dry over Na2SO4, filter, and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (45 g, pre-packed cartridge) eluting with hexane/EtOAc (1:0 to 1:1 gradient over 60 min, 80 mL/min) to obtain the desired intermediate as a colorless oil (1.21 g, 54%). MS (APCI+) m/z: 217 (M+H)+.

Workup

  1. temperatureCool the mixture to room temperature
  2. extractionExtract the aqueous phase with diethyl ether (3×25 mL)
  3. washWash the combined organic extracts with brine (20 mL)
  4. dry with materialdry over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify the crude mixture by chromatography on silica gel (45 g, pre-packed cartridge)
  8. washeluting with hexane/EtOAc (1:0 to 1:1 gradient over 60 min, 80 mL/min)

Sources & evidence

ORD record
ord-78b16d79bcd74f5d85d6bfb27cb2db93
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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