Tetrahydrofuran → 2-(4-Tert-butyl-3.5-difluorophenoxy)-N-((1R)-1-{3-methyl-4-[(methylsulfonyl)amino]phenyl}ethyl)acetamide

HRID 230587

Reaction equation

HRID 230587 reaction equation
O1CCCC1.[C:6]([C:10]1[C:20]([F:21])=[CH:19][C:13]([O:14][CH2:15][C:16]([OH:18])=O)=[CH:12][C:11]=1[F:22])([CH3:9])([CH3:8])[CH3:7].[Cl-].ClC1N(C)CC[NH+]1C.Cl.[NH2:33][C@@H:34]([C:36]1[CH:41]=[CH:40][C:39]([NH:42][S:43]([CH3:46])(=[O:45])=[O:44])=[C:38]([CH3:47])[CH:37]=1)[CH3:35]>C(N(CC)CC)C>[C:6]([C:10]1[C:11]([F:22])=[CH:12][C:13]([O:14][CH2:15][C:16]([NH:33][C@@H:34]([C:36]2[CH:41]=[CH:40][C:39]([NH:42][S:43]([CH3:46])(=[O:45])=[O:44])=[C:38]([CH3:47])[CH:37]=2)[CH3:35])=[O:18])=[CH:19][C:20]=1[F:21])([CH3:7])([CH3:8])[CH3:9]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 109867151H-Imidazolium, 2-chloro-4,5-dihydro-1,3-dimethyl-, chlorideHCID 21097519N-{4-[(1R)-1-aminoethyl]-2-methylphenyl)methanesulfonamide hydrochlorideHCID 68804332(4-tert-Butyl-3,5-difluorophenoxy)acetic acid

Product 1

HCID 577629212-(4-Tert-butyl-3.5-difluorophenoxy)-N-((1R)-1-{3-methyl-4-[(methylsulfonyl)amino]phenyl}ethyl)acetamideYield 38%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a tetrahydrofuran (THF) (3.0 ml) solution of (4-tert-butyl-3,5-difluorophenoxy)acetic acid (166 mg, 0.68 mmol) was added 2-chloro-1,3-dimethylimidazolinium chloride (CDI) (110 mg, 0.68 mmol) at room temperature and the mixture was stirred for 2 hours, followed by the addition of triethylamine (0.5 ml) and N-{4-[(1R)-1-aminoethyl]-2-methylphenyl}methanesulfonamide hydrochloride (180 mg, 0.68 mmol) with stirring for 10 hours. The reaction was partitioned with water and dichloromethane and the organic layer was separated and dried over sodium sulfate. Then filtration and evaporation under reduced pressure gave the crude residue which was purified by silica gel column chromatography, eluting with dichloromethane/methanol from 5:1 to 5:2, to furnish 1 16mg (38%) of the title compound as a white solid.

Workup

  1. stirringwith stirring for 10 hours
  2. customThe reaction was partitioned with water and dichloromethane
  3. customthe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationThen filtration and evaporation under reduced pressure
  6. customgave the crude residue which
  7. customwas purified by silica gel column chromatography
  8. washeluting with dichloromethane/methanol from 5:1 to 5:2

Sources & evidence

ORD record
ord-8cd4d3c93a2e4b4ebd02aad2480257d9
Source dataset
uspto-grants-2009_07
Patent number
US07566739B2

Linked notes

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