Ammonia → 4-(4-Methoxyphenyl)butanamide

HRID 1516343Notes

Reaction equation

HRID 1516343 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)=[CH:5][CH:4]=1.C[N:16]1CCOCC1.C(=O)=O.ClC(OCC(C)C)=O.N.CO.[Cl-].[Na+]>C(OCC)(=O)C.C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH2:11][C:12]([NH2:16])=[O:14])=[CH:5][CH:4]=1

Participants

10

Reactant 7

HCID 222AmmoniaHCID 280Carbon DioxideHCID 887MethanolHCID 5234Sodium ChlorideHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 782804-(4-Methoxyphenyl)butyric acid

Product 1

HCID 225661754-(4-Methoxyphenyl)butanamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(4-Methoxyphenyl) butyric acid (1) (450 g, 2.32 mole) was combined with dry THF (4 L) and 4-methylmorpholine (268 mL, 2.43 mole) in a 12 L three neck flask with mechanical stirring, an ice-methanol cooling bath and nitrogen atmosphere. Small pieces of dry ice were used to bring the bath temperature below B20° C. Isobutyl chloroformate was added at a rate so as not to exceed an internal temperature of B10° C. After stirring for 30 min. at B10 to B20° C., a 4.7 M solution of ammonia in methanol (990 mL, 4.64 mole) was added in one portion. During the addition, the reaction temperature rose to 0° C. The reaction was allowed to stir for 30 min. and then allowed to stand overnight. The product mixture was transferred to a 22 L separatory funnel with ethyl acetate (6 L), and 10% sodium chloride solution (1.5 L). The layers were separated and the organic solution was washed with 10% sodium chloride solution (4×1 L) and then brine (3×500 mL). The organic layer was dried over sodium sulfate, filtered, evaporated and placed under high vacuum overnight. This afforded 432 g (97%) of the pure amide (117) as an off white solid.

Workup

  1. additionDuring the addition
  2. customrose to 0° C
  3. stirringto stir for 30 min.
  4. waitto stand overnight
  5. customThe layers were separated
  6. washthe organic solution was washed with 10% sodium chloride solution (4×1 L)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customplaced under high vacuum overnight

Sources & evidence

ORD record
ord-aabf6a0a6c444b4ab329d928d1f889a3
Source dataset
uspto-grants-2012_07
Patent number
US08227474B2

Reaction notes

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