Pivalic acid → HCID 178451149, compound

HRID 2272671Notes

Reaction equation

HRID 2272671 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([Br:9])[N:3]=1.[OH:10][C:11]([C@@H:18]1[CH2:23][CH2:22][C@H:21]([C:24]([O:26][CH2:27][CH2:28][CH2:29][CH3:30])=[O:25])[CH2:20][CH2:19]1)([C:13]1[S:14][CH:15]=[CH:16][N:17]=1)[CH3:12].C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C(C)(C)C>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C)C(=O)C>[Br:9][C:4]1[N:3]=[C:2]([C:15]2[S:14][C:13]([C:11]([C@@H:18]3[CH2:23][CH2:22][C@H:21]([C:24]([O:26][CH2:27][CH2:28][CH2:29][CH3:30])=[O:25])[CH2:20][CH2:19]3)([OH:10])[CH3:12])=[N:17][CH:16]=2)[CH:7]=[C:6]([CH3:8])[CH:5]=1

Participants

8

Reactant 4

HCID 6417Pivalic acidHCID 11430Potassium CarbonateHCID 112881742,6-Dibromo-4-methylpyridineHCID 178451152HCID 178451152, compound

Product 1

HCID 178451149HCID 178451149, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a vial were added 2,6-dibromo-4-methylpyridine (121 mg, 0.482 mmol), cis-butyl 4-[1-hydroxy-1-(1,3-thiazol-2-yl)ethyl]cyclohexanecarboxylate (75 mg, 0.241 mmol), potassium carbonate (100 mg, 0.722 mmol), pivalic acid (5.59 μl, 0.048 mmol), tetrakis(triphenylphosphine)palladium(0) (11.1 mg, 9.63 μmol) and N,N-dimethylacetamide (760 μl). The vial was sealed and placed under argon through 3 cycles of evacuation and argon flushing then reacted at 80° C. overnight. The resulting mixture was cooled, diluted with ethyl acetate, filtered through a plug of CELITE and concentrated. The residue was purified by column chromatography on silica gel (0-100% ethyl acetate/hexanes) to afford racemic-cis-butyl 4-{1-[5-(6-bromo-4-methylpyridin-2-yl)-1,3-thiazol-2-yl]-1-hydroxyethyl}-cyclohexanecarboxylate.

Workup

  1. customThe vial was sealed
  2. customthen reacted at 80° C. overnight
  3. temperatureThe resulting mixture was cooled
  4. filtrationfiltered through a plug of CELITE
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-34557774aa334d7f9ee1315bf41f10c6
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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