Ammonium Chloride → Methyl[4-hydroxy-4-(1-methylpiperidin-4-yl)-4,10-dihydro-9-oxa-3-thiabenzo[f]azulen-6-ylsulfanyl]acetate

HRID 389031Notes

Reaction equation

HRID 389031 reaction equation
[Mg].Cl[CH:3]1[CH2:8][CH2:7][N:6]([CH3:9])[CH2:5][CH2:4]1.[O:10]=[C:11]1[C:20]2[CH:21]=[C:22]([S:25][CH2:26][C:27]([O:29][CH3:30])=[O:28])[CH:23]=[CH:24][C:19]=2[O:18][CH2:17][C:16]2[CH:15]=[CH:14][S:13][C:12]1=2.[Cl-].[NH4+]>C1COCC1>[CH3:30][O:29][C:27](=[O:28])[CH2:26][S:25][C:22]1[CH:23]=[CH:24][C:19]2[O:18][CH2:17][C:16]3[CH:15]=[CH:14][S:13][C:12]=3[C:11]([OH:10])([CH:3]3[CH2:8][CH2:7][N:6]([CH3:9])[CH2:5][CH2:4]3)[C:20]=2[CH:21]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 793424-chloro-N-methylpiperidineHCID 5462224MagnesiumHCID 86649442Methyl (4-oxo-4,10-dihydro-9-oxa-3-thiabenzo[f]azulen-6-ylsulfanyl)acetate

Product 1

HCID 86649443Methyl[4-hydroxy-4-(1-methylpiperidin-4-yl)-4,10-dihydro-9-oxa-3-thiabenzo[f]azulen-6-ylsulfanyl]acetateYield 18.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A Grignard reagent prepared from magnesium (2.8 g, 116 mmol), 4-chloro-1-methylpiperidine (15.5 mL, 116 mmol), and THF (180 mL) was ice-cooled, and a THF (120 mL) solution of the compound obtained in Example 22 (18.5 g, 58 mmol) was added dropwise thereto. After allowing the mixture to react for 30 minutes, a saturated ammonium chloride was added thereto, and a product was extracted with ethyl acetate. The organic layer was sequentially washed with a saturated ammonium chloride and with a saturated sodium chloride solution, and then dried over anhydrous sodium sulfate, and the solvents were distilled off under a reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:2), to give 4.4 g (18%) of the captioned compound.

Workup

  1. temperaturecooled
  2. customto react for 30 minutes
  3. extractiona product was extracted with ethyl acetate
  4. washThe organic layer was sequentially washed with a saturated ammonium chloride and with a saturated sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationthe solvents were distilled off under a reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:2)

Sources & evidence

ORD record
ord-71015e548e9f4466907a938e1e69e804
Source dataset
uspto-grants-2013_02
Patent number
US08377967B2

Reaction notes

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