Dimethylformamide → HCID 71502739, compound

HRID 1627603Notes

Reaction equation

HRID 1627603 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 95.5%

Conditions

Temperature
110 °C

Procedure

94.6 g (0.3 mol) 4-(4-Cyano-3-methyl-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester, 87.6 mL (0.66 mol) N,N-Dimethylformamide dimethylacetal, 109 mL (1.32 mol) pyrrolidine and 60.4 mL DMF (0.78 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 h. The temperature was brought to 120° C. and kept at this temperature for 7.5 h. Heating was discontinued and the mixture was chilled to ambient temperature. Then, 200 mL water and 400 mL isopropanol were added. The mixture was stirred for 3 h at ambient temperature and 1 h at 5° C. to precipitate the product. The solid was collected rinsed with isopropanol/water (70/30) collected and dried to yield 113.7 g (yield 95.5%, purity 93.3%) 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 h
  4. customwas brought to 120° C.
  5. waitkept at this temperature for 7.5 h
  6. temperatureHeating
  7. temperaturethe mixture was chilled to ambient temperature
  8. additionThen, 200 mL water and 400 mL isopropanol were added
  9. customto precipitate the product
  10. customThe solid was collected
  11. washrinsed with isopropanol/water (70/30)
  12. customcollected
  13. customdried

Sources & evidence

ORD record
ord-e3bdc1aef95340bfb5daae60ad248acb
Source dataset
uspto-grants-2014_07
Patent number
US08785642B2

Reaction notes

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