(Bromomethyl)cyclobutane → HCID 178490690, compound

HRID 78523Notes

Reaction equation

HRID 78523 reaction equation
[C:1]([C:4]1[S:8][C:7]([NH:9][C:10](=[O:20])[C:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=2[O:18][CH3:19])=[N:6][C:5]=1[CH3:21])(=[O:3])[CH3:2].Br[CH2:23][CH:24]1[CH2:27][CH2:26][CH2:25]1.CC(C)([O-])C.[K+]>CN(C)C=O>[C:1]([C:4]1[S:8]/[C:7](=[N:9]\[C:10](=[O:20])[C:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=2[O:18][CH3:19])/[N:6]([CH2:23][CH:24]2[CH2:27][CH2:26][CH2:25]2)[C:5]=1[CH3:21])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 2734658(Bromomethyl)cyclobutaneHCID 23665647Potassium tert-butoxideHCID 35760808N-(5-acetyl-4-methylthiazol-2-yl)-5-chloro-2-methoxybenzamide

Product 1

HCID 178490690HCID 178490690, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of the product of Example 238A (0.75 g, 2.3 mmol), (bromomethyl)cyclobutane (0.31 mL, 2.8 mmol), and potassium t-butoxide (0.41 g, 3.5 mmol) in 7 mL N,N-dimethylformamide was warmed to 65° C. and stirred for 16 hours. The mixture was cooled to ambient temperature, quenched with 5 mL of saturated aqueous NH4Cl and diluted with 10 mL of ethyl acetate. The layers were separated and the aqueous phase was extracted twice with 7 mL of ethyl acetate. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification via column chromatography (SiO2, 40% hexanes in ethyl acetate) afforded the title compound. 1H NMR (300 MHz, CD3OD) δ ppm 1.88-2.15 (m, 6H), 2.51 (s, 3H), 2.75 (s, 3H), 2.83-2.96 (m, 1H), 3.89 (s, 3H), 4.46 (d, J=7.5 Hz, 2H), 7.11 (d, J=9.2 Hz, 1H), 7.45 (dd, J=8.8, 2.7 Hz, 1H), 7.99 (d, J=3.1 Hz, 1H); MS (DCI/NH3) m/z 393 (M+H)+. Anal. Calculated for C19H21ClN2O3S: C, 58.08; H, 5.39; N, 7.13. Found: C, 58.06; H, 5.20; N, 7.06.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customquenched with 5 mL of saturated aqueous NH4Cl
  3. additiondiluted with 10 mL of ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted twice with 7 mL of ethyl acetate
  6. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification via column chromatography (SiO2, 40% hexanes in ethyl acetate)

Sources & evidence

ORD record
ord-c40253908f014a12aa5e7811cd83c076
Source dataset
uspto-grants-2014_09
Patent number
US08841334B2

Reaction notes

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