Hydrochloric Acid → 4-[4-(3-Piperazin-1-ylpropoxy)phenyl]tetrahydropyran-4-carbonitrile

HRID 272909Notes

Reaction equation

HRID 272909 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3([C:30]#[N:31])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[CH:20][CH:19]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.CO.Cl>O1CCOCC1>[N:11]1([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]3([C:30]#[N:31])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[CH:22][CH:23]=2)[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 598375064-{3-[4-(4-Cyano-tetrahydro-pyran-4-yl)-phenoxy]-propyl}-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 598373994-[4-(3-Piperazin-1-ylpropoxy)phenyl]tetrahydropyran-4-carbonitrileYield 72%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

4-{3-[4-(4-Cyano-tetrahydro-pyran-4-yl)-phenoxy]-propyl}-piperazine-1-carboxylic acid tert-butyl ester (500 mg, 1.16 mmol), MeOH (5 ml), 1,4-dioxane (1 ml) and HCl in dioxane (4M, 1.8 ml) was stirred at ambient temperature overnight. The reaction mixture was concentrated in vacuo at 40° C., and diluted with TBME (5 ml). Aqueous NaOH (2M solution) was added to attain a pH of 14 and the mixture separated and extracted with TBME (2×5 ml). The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo to provide title compound as a yellow oil (275 mg, 72%). 1H NMR (400 MHz, CDCl3), δ 7.38 (d, 2H), 6.93 (d, 2H), 4.11-4.05 (m, 2H), 4.03 (t, 2H), 3.89 (td, 2H), 2.90 (t, 4H), 2.51 (t, 2H), 2.44 (br s, 4H), 2.15-2.00 (m, 4H), 1.97 (m, 2H), 1.74 (br s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo at 40° C.
  2. additiondiluted with TBME (5 ml)
  3. additionAqueous NaOH (2M solution) was added
  4. customthe mixture separated
  5. extractionextracted with TBME (2×5 ml)
  6. dry with materialThe combined organic extracts were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b2a53c3ed17b4cda9abb10b797de8e47
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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