Hydrochloric Acid → (alphaR,betaR)-beta-ethyl-N,N,alpha-trimethyl-3-(phenylmethoxy)benzenepropanamide

HRID 1771008Notes

Reaction equation

HRID 1771008 reaction equation
[CH2:1]([C@@H:3]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:10]=1)[C@@H:4]([CH3:8])[C:5](O)=[O:6])[CH3:2].C(Cl)(=O)C(Cl)=O.Cl.[CH3:30][NH:31][CH3:32].C(N(CC)CC)C.Cl>ClCCl>[CH2:1]([C@@H:3]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:10]=1)[C@@H:4]([CH3:8])[C:5]([N:31]([CH3:32])[CH3:30])=[O:6])[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 65578Oxalyl chlorideHCID 60164736(alphaR,betaR)-beta-ethyl-alpha-methyl-3-(phenylmethoxy)benzenepropanoic acid

Product 1

HCID 60164737(alphaR,betaR)-beta-ethyl-N,N,alpha-trimethyl-3-(phenylmethoxy)benzenepropanamideYield 95.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

The product of Example 4 (3 g, 10 mmol) was dissolved in dichloromethane (10 ml), oxalyl chloride (2.6 ml, 30 mmol) was added dropwise, and it was reacted at room temperature for 1 hr, then the reaction solution was concentrated to give a pale yellow oil which was further dissolved in dichloromethane. And then the resulted solution was added dropwise to an ice-water bath cooled solution of dimethylamine hydrochloride (1.6 g, 20 mmol) and triethylamine (4.3 ml, 30 mmol) in dichloromethane, then the mixture was slowly warmed to room temperature to react for 1 hour. The pH thereof was adjusted to about 7 with 1N hydrochloric acid, then it was extracted with dichloromethane. The organic phases were combined, washed with saturated sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate, concentrated and recrystallized with petroleum ether and ethyl acetate to give a white solid 3.1 g, yield: 95%. 1HNMR (300 MHz, CDCl3): δ 7.3-7.5 (5H, m), 7.2 (1H, m), 6.7-6.8 (3H, m), 5.0 (2H, s), 2.8-2.9 (1H, m), 2.7-2.8 (1H, m), 2.6 (3H, s), 2.5 (3H, s), 1.8-1.9 (1H, m), 1.4-1.6 (1H, m), 1.1 (3H, d, J=6.2), 0.8 (3H, t, J=6.8, 14.1). ESI-MS: 326.4 (M+H).

Workup

  1. customit was reacted at room temperature for 1 hr
  2. concentrationthe reaction solution was concentrated
  3. customto give a pale yellow oil which
  4. additionAnd then the resulted solution was added dropwise to an ice-water bath
  5. customto react for 1 hour
  6. extractionit was extracted with dichloromethane
  7. washwashed with saturated sodium bicarbonate solution and saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated
  10. customrecrystallized with petroleum ether and ethyl acetate

Sources & evidence

ORD record
ord-ecc95838156f4899b0ddc520338d7731
Source dataset
uspto-grants-2016_02
Patent number
US09249084B2

Reaction notes

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