Dimethylformamide → HCID 71502739, compound

HRID 1627604Notes

Reaction equation

HRID 1627604 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[C:17]([CH3:23])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO[CH:26](OC)[N:27]([CH3:29])[CH3:28].N1CC[CH2:34][CH2:33]1.CN(C=O)C>>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[C:17](/[CH:23]=[CH:29]/[N:27]3[CH2:26][CH2:34][CH2:33][CH2:28]3)[CH:16]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 31268PyrrolidineHCID 78373Dimethylformamide dimethyl acetalHCID 44128630HCID 44128630, compound

Product 1

HCID 71502739HCID 71502739, compoundYield 93.1%

Conditions

Temperature
110 °C

Procedure

47.3 g (0.15 mol) 4-(4-Cyano-3-methyl-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester, 43.8 mL (0.33 mol) N,N-Dimethylformamide dimethylacetal, 54.6 mL (0.66 mol) pyrrolidine and 30.2 mL DMF (0.39 mol) were mixed and the mixture was heated within 30 min to 90° C. and kept at this temperature for 1 h. All volatile content was allowed to distil off. The temperature was raised to 110° C. and kept at this temperature for 2.5 h. The temperature was brought to 120° C. and kept at this temperature for 5 h. Heating was discontinued and the mixture was chilled to ambient temperature, diluted with 400 mL MTB ether and washed twice with 200 mL saturated aqueous NaHCO3 and once with 200 mL water. The organic layer was concentrated and recrystallized from isopropanol/water (245 mL/105 mL) collected and dried to yield 55.5 g (yield 93%, purity 100%) of 4-[4-Cyano-3-((E)-2-pyrrolidin-1-yl-vinyl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester

Workup

  1. temperaturethe mixture was heated within 30 min to 90° C.
  2. customto distil off
  3. waitkept at this temperature for 2.5 h
  4. customwas brought to 120° C.
  5. waitkept at this temperature for 5 h
  6. temperatureHeating
  7. temperaturethe mixture was chilled to ambient temperature
  8. additiondiluted with 400 mL MTB ether
  9. washwashed twice with 200 mL saturated aqueous NaHCO3 and once with 200 mL water
  10. concentrationThe organic layer was concentrated
  11. customrecrystallized from isopropanol/water (245 mL/105 mL)
  12. customcollected
  13. customdried

Sources & evidence

ORD record
ord-463e9449867c4005a5a074d3774932cf
Source dataset
uspto-grants-2014_07
Patent number
US08785642B2

Reaction notes

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