Triethylamine → 4-(4-Bromo-2-methylphenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 533514Notes

Reaction equation

HRID 533514 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([CH3:18])([S:14]([CH3:17])(=[O:16])=[O:15])[C:11]([OH:13])=O)=[C:4]([CH3:19])[CH:3]=1.[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:26][NH2:27].O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>ClCCl.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([CH3:18])([S:14]([CH3:17])(=[O:16])=[O:15])[C:11]([NH:27][O:26][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25][O:20]2)=[O:13])=[C:4]([CH3:19])[CH:3]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 665779334-(4-Bromo-2-methylphenyl)-2-methyl-2-(methylsulfonyl)butanoic acid

Product 1

HCID 866687554-(4-Bromo-2-methylphenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideYield 50.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

4-(4-Bromo-2-methylphenyl)-2-methyl-2-(methylsulfonyl)butanoic acid (3.28 g, 9.39 mmol), O-tetrahydro-2H-pyran-2-yl-hydroxylamine (2.19 g, 18.7 mmol), 1-hydroxy benzotriazole monohydrate (3.68 g, 24 mmol), triethylamine (3.35 mL, 24 mmol) and (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.59 g, 18.7 mmol) were combined followed by the addition 60 mL of dichloromethane. The reaction was allowed to stir at room temperature overnight. The reaction mixture was diluted with 20 mL of dichloromethane and 60 mL of water. The aqueous layer was extracted with dichloromethane (2×40 mL). The organics were combined, dried over magnesium sulfate, filtered and concentrated onto silica gel. Silica chromatography (30% ethyl acetate 70% heptane for 10 minutes, then 30% ethyl acetate 70% heptane to 60% ethyl acetate 40% heptane for 40 minutes) afforded the title compound as a white solid (2.11 g, 50.1%).

Workup

  1. extractionThe aqueous layer was extracted with dichloromethane (2×40 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated onto silica gel
  5. waitSilica chromatography (30% ethyl acetate 70% heptane for 10 minutes

Sources & evidence

ORD record
ord-9f1c28446b9e43c0bea2e1a6f7217152
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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