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

HRID 533521Notes

Reaction equation

HRID 533521 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([S:15]([CH3:18])(=[O:17])=[O:16])([CH3:14])[C:11]([OH:13])=O)=[C:4]([F: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]([CH3:14])([S:15]([CH3:18])(=[O:17])=[O:16])[C:11]([NH:27][O:26][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25][O:20]2)=[O:13])=[C:4]([F: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 665779184-(4-Bromo-2-fluoro-phenyl)-2-methanesulfonyl-2-methyl-butyric acid

Product 1

HCID 866687574-(4-Bromo-2-fluorophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideYield 79.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

4-(4-Bromo-2-fluoro-phenyl)-2-methanesulfonyl-2-methyl-butyric acid (1.96 g, 5.55 mmol), O-tetrahydro-2H-pyran-2-yl-hydroxylamine (0.910 g, 7.77 mmol), 1-hydroxy benzotriazole monohydrate (1.53 g, 9.99 mmol), triethylamine (1.39 mL, 9.99 mmol) and 1, (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.49 g, 7.77 mmol) were combined followed by the addition 60 mL of dichloromethane. The reaction was allowed to stir at room temperature overnight, was then diluted with 20 mL of dichloromethane and 60 mL of water. The aqueous layer was re-extracted with DCM (2×40 mL). The organics were combined, dried over magnesium sulfate, filtered and concentrated onto silica gel. Silica chromatography (40% ethyl acetate 60% heptane to 40% ethyl acetate 60% heptane to 80% ethyl acetate 20% heptane for 60 minutes) afforded the title compound as a white foam 2.0 g, (79.9%). LC-MS m/z 452.1 (M−1)

Workup

  1. extractionThe aqueous layer was re-extracted with DCM (2×40 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-185b4f59ea054aeebe04b06c8fa276f7
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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