Triethylamine → (3S)-3-(benzyloxy)-N-methoxy-N-methylbutanamide

HRID 238945Notes

Reaction equation

HRID 238945 reaction equation
[CH2:1]([O:8][C@@H:9]([CH3:14])[CH2:10][C:11]([OH:13])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:16][NH:17][O:18][CH3:19].C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C>[CH2:1]([O:8][C@@H:9]([CH3:14])[CH2:10][C:11]([N:17]([O:18][CH3:19])[CH3:16])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11845529(S)-3-(Benzyloxy)butanoic acid

Product 1

HCID 86658651(3S)-3-(benzyloxy)-N-methoxy-N-methylbutanamideYield 75.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under a nitrogen atmosphere, to a solution of the above (3S)-3-(benzyloxy)butanoic acid (225 g) in DMF (1.5 L), N,O-dimethylhydroxylamine hydrochloride (111 g, 1.1 mol) and triethylamine (0.32 mL, 2.3 mol) were added, and the mixture was stirred at room temperature for 40 minutes. Subsequently, 1-hydroxybenzotriazole (112 g, 0.83 mol) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (160 g, 0.83 mol) were successively added, and the mixture was stirred at room temperature for 5 hours. After the reaction, the reaction mixture was poured to ice-water, and it was extracted with diethyl ether. After it was successively washed with 1N hydrochloric acid, water, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, it was dried with sodium sulfate and the solvent was distilled off under reduced pressure to give (3S)-3-(benzyloxy)-N-methoxy-N-methylbutanamide (196 g) as a mixture. The present compound was used for the subsequent reaction without further purification.

Workup

  1. stirringthe mixture was stirred at room temperature for 5 hours
  2. customAfter the reaction
  3. extractionwas extracted with diethyl ether
  4. washAfter it was successively washed with 1N hydrochloric acid, water
  5. dry with materiala saturated aqueous sodium hydrogencarbonate solution and saturated brine, it was dried with sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-e7a1ba0f82484c3cab1353d64f3faac4
Source dataset
uspto-grants-2014_02
Patent number
US08642640B2

Reaction notes

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