1-Hydroxybenzotriazole → 4-[4-(ethylsulfonyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-one

HRID 1881854Notes

Reaction equation

HRID 1881854 reaction equation
[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]([CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:13](O)=[O:14])=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2].Cl.CONC.Cl.CN(C)[CH2:31][CH2:32]CN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O.O.C(N(CC)CC)C>[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]([CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:13](=[O:14])[CH:31]=[CH2:32])=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 210939922-[4-(ethylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid

Product 1

HCID 593315624-[4-(ethylsulfonyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-oneYield 90%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 2-[4-(ethylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)propanoic acid (1.30 g) in N,N-dimethylformamide (20 mL) were added N-methoxymethanamine hydrochloride (582 mg), triethylamine (1.67 mL), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (840 mg) and 1-hydroxybenzotriazole (670 mg), and the mixture was stirred at room temperature for 3 days. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50-0:100, volume ratio) to give a colorless oil. A solution of the obtained oil in tetrahydrofuran (40 mL) was purged with nitrogen, and a 1.0M vinylmagnesium bromide tetrahydrofuran solution (12 mL) was added under ice-cooling. The reaction solution was warmed to room temperature, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was added to 1M hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=20:80-80:20, volume ratio) to give the title compound (1.20 g, yield 90%) as a colorless oil. MS: 337 (MH+).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed successively with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50-0:100, volume ratio)
  6. customto give a colorless oil
  7. customA solution of the obtained oil in tetrahydrofuran (40 mL) was purged with nitrogen
  8. additiona 1.0M vinylmagnesium bromide tetrahydrofuran solution (12 mL) was added under ice-
  9. temperaturecooling
  10. temperatureThe reaction solution was warmed to room temperature
  11. stirringthe mixture was stirred at room temperature for 1 hr
  12. additionThe reaction mixture was added to 1M hydrochloric acid
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe extract was washed successively with water and saturated brine
  15. dry with materialdried over anhydrous magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=20:80-80:20, volume ratio)

Sources & evidence

ORD record
ord-ad49bd302eb146b9b6b244915994c5b9
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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