4-Methylmorpholine → Tert-butyl 4-carbamoyl-2-methyl-benzoate

HRID 1522788Notes

Reaction equation

HRID 1522788 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[CH:10][C:9]=1[CH3:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:19]1CCOCC1.C(OC(Cl)=O)C(C)C.[OH-].[NH4+]>O1CCCC1.O>[C:12]([C:11]1[CH:15]=[CH:16][C:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[C:9]([CH3:17])[CH:10]=1)(=[O:13])[NH2:19]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 14923Ammonium HydroxideHCID 62365Isobutyl chloroformateHCID 894448004-(tert-Butoxycarbonyl)-3-methylbenzoic acid

Product 1

HCID 67246890Tert-butyl 4-carbamoyl-2-methyl-benzoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-tert-butoxycarbonyl-3-methyl-benzoic acid (40 g) was suspended in tetrahydrofuran (160 mL). This solution was cooled to −30 C then N-methyl morpholine (18.7 mL) followed by isobutylchloroformate (24.2 mL) were added. A white precipitate appeared. The solution was stirred for 8 hours then a solution of ammonium hydroxide (100 mL) was added. The reaction mixture was slowly allowed to warm to room temperature over 48 hours. Then water was added and the mixture was extracted with ethyl acetate. The organic extract was washed with water, dried over sodium sulfate and concentrated to give a solid which was further triturated with a mixture of dichloromethane/ethyl acetate, filtered, to give tert-butyl 4-carbamoyl-2-methyl-benzoate (29.9 g) as a white solid. 1H-NMR (CDCl3, 400 MHz): 7.90 (d, 1 H), 7.72 (s, 1 H), 7.65 (d, 1 H), 2.63 (s, 3 H), 1.62 (s, 9 H).

Workup

  1. temperatureThis solution was cooled to −30 C
  2. additionwere added
  3. extractionthe mixture was extracted with ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customto give a solid which
  9. customwas further triturated with a mixture of dichloromethane/ethyl acetate
  10. filtrationfiltered

Sources & evidence

ORD record
ord-6bfda8df8b634e08ad1a2bfc561b685d
Source dataset
uspto-grants-2015_07
Patent number
US09078444B2

Reaction notes

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