4-Methylmorpholine → (S)-2-(dibenzylamino)-N-methoxy-N-methylpentanamide

HRID 1099510Notes

Reaction equation

HRID 1099510 reaction equation
[CH2:1]([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C@@H:9]([CH2:13][CH2:14][CH3:15])[C:10](O)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1.Cl.[CH3:53][NH:54][O:55][CH3:56]>ClCCl.O>[CH2:1]([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C@@H:9]([CH2:13][CH2:14][CH3:15])[C:10]([N:54]([O:55][CH3:56])[CH3:53])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 44223289HCID 44223289, compound

Product 1

HCID 44223340(S)-2-(dibenzylamino)-N-methoxy-N-methylpentanamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

(S)-2-(dibenzylamino)pentanoic acid (1.57 Kg; 5.286 mol) was dissolved in dry dichloromethane (9.42 L) under a nitrogen atmosphere and cooled to 0-5° C. The resulting solution was treated with N-hydroxybenzotriazole (HOBt; 928 g; 6.875 mol) followed by 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 1.51 Kg; 7.931 mol;) at 0-5° C. The reaction mixture was stirred for 3 hours at ambient temperature, then treated with N-methylmorpholine (NMM; 1.62 Kg; 16.07 mol) followed by N,O-dimethylhydroxylamine hydrochloride (1.29 Kg; 13.22 mol) at 0° C. The reaction mixture was stirred at ambient temperature for 15 hours, then water (2.5 L) added, and the mixture stirred for 10 minutes. The organic layer was separated, washed with 1% aqueous hydrochloric acid, followed by saturated aqueous sodium bicarbonate, then brine solution. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure to provide (S)-2-(dibenzylamino)-N-methoxy-N-methylpentanamide, a compound of formula (6), as a syrupy oil.

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 15 hours
  2. stirringthe mixture stirred for 10 minutes
  3. customThe organic layer was separated
  4. washwashed with 1% aqueous hydrochloric acid
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a11a438e74494d9db70a1a24763156e3
Source dataset
uspto-grants-2012_03
Patent number
US08143448B2

Reaction notes

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