Thionyl Chloride → HCID 67486383, compound

HRID 1755152Notes

Reaction equation

HRID 1755152 reaction equation
[Br:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:8][CH:7]=1)[C:3]([OH:5])=O.O=S(Cl)Cl.[CH:20]1([CH2:26][O:27][C:28]2[CH:33]=[CH:32][C:31]([NH2:34])=[CH:30][CH:29]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.C(N(C(C)C)C(C)C)C>C1(C)C=CC=CC=1>[Br:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:8][CH:7]=1)[C:3]([NH:34][C:31]1[CH:30]=[CH:29][C:28]([O:27][CH2:26][CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)=[CH:33][CH:32]=1)=[O:5]

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 156816514-(Cyclohexylmethoxy)anilineHCID 86669781HCID 86669781, compound

Product 1

HCID 67486383HCID 67486383, compoundYield 59.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
90 °C

Procedure

To a stirring solution of bromo-(4-tert-butyl-phenyl)-acetic acid (1.2 g, 4.43 mmol) in toluene (20 mL) was added SOCl2 (0.8 mL, 11.1 mmol). The mixture was stirred at 90° C. for 1 hr and concentrated under reduced pressure. This crude product was dissolved into toluene (20 ml), and 4-cyclohexylmethoxy-phenylamine (0.91 g, 4.43 mmol) and ethyl-diisopropyl-amine (0.85 mL, 4.87 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 1 hr. The reaction mixture was quenched with water and diluted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel, eluting with ethyl acetate-hexanes (3:7) to afford 2-bromo-2-(4-tert-butyl-phenyl)-N-(4-cyclohexylmethoxy-phenyl)-acetamide as a brown oil (1.2 g, 59%): 1H NMR (300 MHz, DMSO-d6): δ 10.35 (s, 1H) 7.49 (m, 6H), 6.87 (d, J=9.3 Hz, 2H), 5.74 (s, 1H), 3.75 (d, J=6.3 Hz, 2H), 1.69 (m, 6H), 1.27 (m, 12H), 1.09 (m, 2H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionwere added at room temperature
  3. stirringThe reaction mixture was stirred at room temperature for 1 hr
  4. customThe reaction mixture was quenched with water
  5. additiondiluted with EtOAc
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography on silica gel
  10. washeluting with ethyl acetate-hexanes (3:7)

Sources & evidence

ORD record
ord-2b45ba2d39fd4d6b8ca9cee3e77f6333
Source dataset
uspto-grants-2015_10
Patent number
US09169201B2

Reaction notes

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