Hydrochloric Acid → 3-(5-Fluoro-2-methylphenyl)-3-methyl-1-morpholin-4-ylbutan-1-one

HRID 400620Notes

Reaction equation

HRID 400620 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:15])=[C:6]([C:8]([CH3:14])([CH3:13])[CH2:9][C:10]([OH:12])=O)[CH:7]=1.O=S(Cl)Cl.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.N1C=CC=CC=1.Cl>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:15])=[C:6]([C:8]([CH3:14])([CH3:13])[CH2:9][C:10]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[O:12])[CH:7]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 8083MorpholineHCID 24386Thionyl ChlorideHCID 585095523-(5-Fluoro-2-methylphenyl)-3-methylbutanoic acid

Product 1

HCID 600266843-(5-Fluoro-2-methylphenyl)-3-methyl-1-morpholin-4-ylbutan-1-oneYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 3-(5-fluoro-2-methylphenyl)-3-methylbutyric acid (3.80 g, 18.0 mmol) in 15 mL of dichloromethane was treated with SOCl2 (1.98 mL, 27.1 mmol) at 0° C. After 30 minutes, a mixture of morpholine (2.36 mL, 27.1 mmol) and pyridine (4.4 mL, 54.2 mmol) in 10 mL of dichloromethane was added to the reaction mixture at 0° C. After an additional 90 minutes, 60 mL of 2 M aqueous HCl solution was added, phases were separated and the aqueous layer was extracted with three 50 mL portions of dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated in vacuo to give 5.03 g of 3-(5-fluoro-2-methylphenyl)-3-methyl-1-morpholin-4-ylbutan-1-one as an oil, which was used without further purification (quantitative yield).

Workup

  1. additionwas added to the reaction mixture at 0° C
  2. waitAfter an additional 90 minutes
  3. customphases were separated
  4. extractionthe aqueous layer was extracted with three 50 mL portions of dichloromethane
  5. dry with materialThe combined organic phases were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-413f9bb6dc89431f87ec33b1bb4c112e
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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