Acetic Acid → 2-(Methylamino)-2-phenylbutyl 3,4,5-trimethoxybenzoate

HRID 1445960Notes

Reaction equation

HRID 1445960 reaction equation
[CH3:1][NH:2][C:3]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH2:6][CH3:7])[CH2:4][OH:5].[Li]CCCC.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH:27]=[C:28]([O:32][CH3:33])[C:29]=1[O:30][CH3:31])[C:24](Cl)=[O:25].C(O)(=O)C>C1COCC1>[CH3:7][CH2:6][C:3]([NH:2][CH3:1])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:4][O:5][C:24]([C:23]1[CH:27]=[C:28]([O:32][CH3:33])[C:29]([O:30][CH3:31])=[C:21]([O:20][CH3:19])[CH:22]=1)=[O:25]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 107260432-Methylamino-2-phenylbutanolHCID 178418339Butyllithium

Product 1

HCID 1347482-(Methylamino)-2-phenylbutyl 3,4,5-trimethoxybenzoateYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1.84 g of 8 (10.3 mmol) in 28 mL of anhydrous THF were added dropwise, at −78° C., 4.11 mL of n-BuLi (2.5 mol/L in hexanes). After 15 minutes, a solution of 2.31 g (10.01 mmol) of 3,4,5-trimethoxybenzoyl chloride in 15.8 mL of anhydrous THF was added. The reaction mixture was then allowed to warm to −30° C. (ca 1 h) and 19 mL of acetic acid were cautiously added. Solvents were removed under vacuum and 55 mL of diethyl ether and 55 mL of water were added to the previously obtained oil. After stirring until complete dissolution, the resulting mixture was then decanted and the aqueous layer alcalinized completely with solid Na2CO3 and re-extracted with diethyl ether. The organic layers were washed twice with a saturated aqueous solution of sodium carbonate and with brine and then dried over sodium sulphate. Diethyl ether was evaporated under vacuum and the ester 9 was purified by chromatography on silica gel column (ethyl acetate/n-hexane, 7:3) to give 1.4 g of pure N-desmethyltrimebutine 9 (49% yield) as a yellow pale oil. MS(ESI), m/e 374.1 (M+).

Workup

  1. additionwere cautiously added
  2. customSolvents were removed under vacuum and 55 mL of diethyl ether and 55 mL of water
  3. additionwere added to the previously obtained oil
  4. customthe resulting mixture was then decanted
  5. extractionre-extracted with diethyl ether
  6. washThe organic layers were washed twice with a saturated aqueous solution of sodium carbonate and with brine
  7. dry with materialdried over sodium sulphate
  8. customDiethyl ether was evaporated under vacuum
  9. customthe ester 9 was purified by chromatography on silica gel column (ethyl acetate/n-hexane, 7:3)

Sources & evidence

ORD record
ord-98cdac819f6d4314933b94913a39a692
Source dataset
uspto-grants-2010_02
Patent number
US07666907B2

Reaction notes

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