Potassium Carbonate → 4-[4-(3-Pyrrolidin-1-ylbutoxy)phenyl]tetrahydropyran-4-carbonitrile

HRID 272915Notes

Reaction equation

HRID 272915 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][CH:19]([N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1)[CH3:20].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[N:21]1([CH:19]([CH3:20])[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)[CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 230916094-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrileHCID 230916561-(4-Chlorobutan-2-yl)pyrrolidine

Product 1

HCID 598374724-[4-(3-Pyrrolidin-1-ylbutoxy)phenyl]tetrahydropyran-4-carbonitrileYield 9.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrile (1.0 g, 4.9 mmol), 1-(3-chloro-1-methyl-propyl)-pyrrolidine (780 mg, 3.90 mmol), DMF (20 ml) and K2CO3 (2.71 g, 19.60 mmol) were reacted together according to general procedure E. The organic phase was washed with 2M NaOH (3×20 ml), water (2×20 ml), dried over MgSO4, fitered and concentrated in vacuo at 35° C. and purified by preparative HPLC, eluting with acetonitrile/water/0.1% TFA as a gradient, to provide the title compound (120 mg, 9%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.38 (d, 2H), 6.93 (d, 2H), 4.15-3.98 (m, 4H), 3.89 (td, 2H), 2.75-2.51 (m, 5H), 2.22-1.74 (m, 10H), 1.17 (d, 3H).

Workup

  1. washThe organic phase was washed with 2M NaOH (3×20 ml), water (2×20 ml)
  2. dry with materialdried over MgSO4
  3. concentrationfitered and concentrated in vacuo at 35° C.
  4. custompurified by preparative HPLC
  5. washeluting with acetonitrile/water/0.1% TFA as a gradient

Sources & evidence

ORD record
ord-3a3251d0391a4b459cb1b6ab9778198b
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

Loading…