Ammonia → HCID 178447135, compound

HRID 82776Notes

Reaction equation

HRID 82776 reaction equation
[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11](=[O:23])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=2[OH:22])/[N:7]([CH2:24][C@H:25]2[CH2:29][CH2:28][CH2:27][O:26]2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].N.Br[CH2:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11](=[O:23])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=2[O:22][CH2:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])/[N:7]([CH2:24][C@H:25]2[CH2:29][CH2:28][CH2:27][O:26]2)[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 11430Potassium CarbonateHCID 21642BromopinacoloneHCID 178441326HCID 178441326, compound

Product 1

HCID 178447135HCID 178447135, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of (R,Z)-N-(5-tert-butyl-3-((tetrahydrofuran-2-yl)methyl)thiazol-2(3H)-ylidene)-2-hydroxy-5-(trifluoromethyl)benzamide (isolated as a byproduct from Example 62B; MS (DCI/NH3) m/z 429 (M+H)+) (330 mg, 0.77 mmol), 1-bromo-3,3-dimethylbutan-2-one (165 mg, 0.92 mmol) and potassium carbonate (106 mg, 0.77 mmol) in acetone (20 mL) was warmed to reflux for 36 hours and then concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The acetate layer was washed with brine, dried with MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by chromatography (SiO2, eluted with hexane-EtOAc: 2:1) to afford 255 mg of the title product. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.15-1.20 (m, 9 H), 1.32 (s, 9 H), 1.59-1.70 (m, 1 H), 1.74-2.00 (m, 3 H), 3.61-3.69 (m, 1 H), 3.71-3.84 (m, 1 H), 4.14-4.37 (m, 3 H), 5.30 (s, 2 H), 6.99 (d, J=8.7 Hz, 1 H), 7.26 (s, 1 H), 7.69 (dd, J=8.9, 2.2 Hz, 1 H), 7.97 (d, J=2.8 Hz, 1 H). MS (DCI/NH3) m/z 527 (M+H)+. Anal calculated for C26H33F3N2O4S: C, 59.30; H, 6.32; N, 5.32. Found: C, 59.27; H, 6.59; N, 5.34.

Workup

  1. customisolated as a byproduct from Example 62B
  2. temperatureto reflux for 36 hours
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was partitioned between ethyl acetate and water
  5. washThe acetate layer was washed with brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by chromatography (SiO2, eluted with hexane-EtOAc: 2:1)

Sources & evidence

ORD record
ord-2de6d4823700449d8f0bf3c950f749c8
Source dataset
uspto-grants-2014_09
Patent number
US08846730B2

Reaction notes

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