Dimethylformamide → 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbonitrile

HRID 272856Notes

Reaction equation

HRID 272856 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl[CH2:17][CH2:18][CH2:19][N:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1.CN(C=O)C.C([O-])([O-])=O.[K+].[K+]>Cl.CC(OC)(C)C>[N:20]1([CH2:19][CH2:18][CH2:17][O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 113210281-(3-Chloropropyl)-pyrrolidineHCID 230916094-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrile

Product 1

HCID 598373944-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbonitrileYield 53%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

4-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrile (2 g, 9.86 mmol), 1-(3-chloro-propyl)-pyrrolidine (2.33 g, 15.78 mmol), DMF (40 ml) and K2CO3 (5.45 g, 39.44 mmol) were reacted together according to general procedure E. The crude reaction product was diluted with 2M HCl solution (200 ml) and washed with ethyl acetate (3×50 ml). The aqueous phase was basified to pH 14 with 2M NaOH (200 ml) and extracted with ethyl acetate (4×50 ml). The combined organic extracts were dried over MgSO4, filtered, washed with ethyl acetate and concentrated in vacuo to give a white solid. The solid was slurried in TBME (15 ml) and heptane (15 ml), filtered, washed with heptane (8 ml) and dried on the filter for 2 hours to give the title compound as a white solid (1.6 g, 53%). 1H NMR (400 MHz, DMSO-d6) δ7.43 (d, 2H), 6.99 (d, 2H), 4.08-3.94 (m, 4H), 3.64 (dt, 2H), 2.57-2.47 (m, 2H), 2.46-2.36 (m, 4H), 2.12-1.94 (m, 4H), 1.87 (p, 2H), 1.73-1.62 (m, 4H).

Workup

  1. customThe crude reaction product
  2. washwashed with ethyl acetate (3×50 ml)
  3. extractionextracted with ethyl acetate (4×50 ml)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. washwashed with ethyl acetate
  7. concentrationconcentrated in vacuo
  8. customto give a white solid
  9. filtrationheptane (15 ml), filtered
  10. washwashed with heptane (8 ml)
  11. customdried on the
  12. filtrationfilter for 2 hours

Sources & evidence

ORD record
ord-8de876506fa34535b3c1972de5e8fc98
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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