Sodium;3-oxidodioxaborirane;tetrahydrate → 4-{4-[3-(1-Oxo-thiomorpholin-4-yl)-propoxy]-phenyl}-tetra-hydropyran-4-carbonitrile

HRID 272904Notes

Reaction equation

HRID 272904 reaction equation
B1([O-])OO1.[OH2:5].O.O.O.[Na+].[N:10]1([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3([C:32]#[N:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[CH2:15][CH2:14][S:13][CH2:12][CH2:11]1>C(O)(=O)C>[O:5]=[S:13]1[CH2:14][CH2:15][N:10]([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]3([C:32]#[N:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[CH:24][CH:25]=2)[CH2:11][CH2:12]1

Participants

4

Reactant 2

HCID 23693097Sodium;3-oxidodioxaborirane;tetrahydrateHCID 598374964-[4-(3-Thiomorpholin-4-ylpropoxy)phenyl]tetrahydropyran-4-carbonitrile

Product 1

HCID 598375334-{4-[3-(1-Oxo-thiomorpholin-4-yl)-propoxy]-phenyl}-tetra-hydropyran-4-carbonitrileYield 58%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Sodium perborate tetrahydrate (221 mg, 1.43 mmol) and glacial acetic acid (5 ml) was heated to 50 to 60° C. and 4-[4-(3-Thiomorpholin-4-ylpropoxy)phenyl]tetrahydropyran-4-carbonitrile (500 mg, 1.43 mmol) was added in one portion and the heating was maintained for 3 hours. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was added to ice water (15 ml) and extracted with EtOAc (3×5 ml), which was discarded. The aqueous phase was basified to pH 8-9 with 2M sodium hydroxide and extracted with DCM (3×25 ml), dried over MgSO4, filtered and concentrated in vacuo at 35° C. The crude material was subjected to chromatography on silica eluting with DCM:MeOH:NH3 (97:2:1 to 92:6:2) to provided the title compound (300 mg, 58%) as a white solid. 1H NMR (400 MHz, CDCl3), δ 7.38 (d, 2H), 6.92 (d, 2H), 4.11-4.05 (m, 2H), 4.03 (t, 2H), 3.89 (td, 2H), 3.15-3.03 (m, 2H), 2.94-2.67 (m, 6H), 2.63 (t, 2H), 2.16-1.92 (m, 6H).

Workup

  1. temperaturethe heating was maintained for 3 hours
  2. filtrationfiltered
  3. additionThe filtrate was added to ice water (15 ml)
  4. extractionextracted with EtOAc (3×5 ml), which
  5. extractionextracted with DCM (3×25 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo at 35° C

Sources & evidence

ORD record
ord-5bd80a42f65847d1b1742dd9be8afd00
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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