Diethyl Ether → HCID 68183080, compound

HRID 1615530Notes

Reaction equation

HRID 1615530 reaction equation
[CH3:1][C:2]1([CH3:18])[C:16](=[O:17])[C:6]2[CH:7]=[C:8]([C:10]3[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=3)[S:9][C:5]=2[CH2:4][CH2:3]1.C1COCC1.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([Mg]Br)=[CH:27][CH:26]=1.CCOCC>[NH4+].[Cl-]>[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([C:16]2([OH:17])[C:6]3[CH:7]=[C:8]([C:10]4[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=4)[S:9][C:5]=3[CH2:4][CH2:3][C:2]2([CH3:18])[CH3:1])=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 3283Diethyl Ether3×HCID 8028TetrahydrofuranHCID 68183135HCID 68183135, compoundHCID 178478191HCID 178478191, compound3×

Product 1

HCID 68183080HCID 68183080, compound

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Procedure

In a 100 mL round bottomed flask were placed 5,5-dimethyl-2-pyridin-4-yl-6,7-dihydro-1-benzothiophen-4(5H)-one (380 mg, 1.5 mmol) and THF (30 mL). To the mixture was added a solution of 4-chlorophenylmagnesium bromide in ether (1.0 M, 3.5 mL, 3.5 mmol) then the reaction was stirred for 3 hr at rt. LCMS indicated that starting material still remained, so additional 4-chlorophenylmagnesium bromide in ether (1.0M, 2.5 mL, 2.5 mmol) was added and the reaction was stirred for 16 hr at rt then for 10 hr at 70° C. The mixture was allowed to cool to rt then additional 4-chlorophenylmagnesium bromide in ether (1.0M, 5 mL, 5 mmol) was added and the mixture was stirred for 16 hr at rt. The mixture was then diluted with a saturated aqueous solution of NH4Cl (50 mL) and was extracted with EtOAc (50 mL×2). The combined organic phases were dried over anhydrous MgSO4. The insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified using column chromatography on silica gel (24 g RediSep column, gradient 30% EA in hexane to 100% EA in hexane) to give the product (530 mg; 97%) as a colorless foam: 1H NMR (400 MHz, DMSO-d6) δ: 8.48 (dd, 2H), 7.45 (dd, 2H), 7.32-7.35 (m, 2H), 7.23-7.25 (m, 3H), 5.55 (s, 1H), 2.87-2.91 (m, 2H), 1.84-1.90 (m, 1H), 1.57-1.63 (m, 1H), 0.91 (s, 3H), 0.63 (s, 3H).

Workup

  1. customIn a 100 mL round bottomed flask were placed
  2. stirringthe reaction was stirred for 16 hr at rt
  3. waitfor 10 hr at 70° C
  4. temperatureto cool to rt
  5. stirringthe mixture was stirred for 16 hr at rt
  6. extractionwas extracted with EtOAc (50 mL×2)
  7. dry with materialThe combined organic phases were dried over anhydrous MgSO4
  8. customThe insoluble materials were removed by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified
  11. customto give the product (530 mg; 97%) as a colorless foam

Sources & evidence

ORD record
ord-8dfb5db548674b798f95d82b797f9b69
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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