Bromomethylcyclopropane → HCID 16722640, compound

HRID 2421108Notes

Reaction equation

HRID 2421108 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH2:26])[CH:6]=[CH:7][C:8]=1[C:9]1[O:10][C:11]([C:14]2[C:15]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:16][O:17][C:18]=2[CH3:19])=[N:12][N:13]=1.C(N(CC)[CH:31]([CH3:33])[CH3:32])(C)C.Br[CH2:37][CH:38]1[CH2:40][CH2:39]1.[CH3:41][Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1>[CH:40]1([CH2:39][CH2:19][C:18]2[O:17][N:16]=[C:15]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:14]=2[C:11]2[O:10][C:9]([C:8]3[CH:7]=[CH:6][C:5]([NH:26][CH2:41][CH:31]4[CH2:33][CH2:32]4)=[CH:4][C:3]=3[O:2][CH3:1])=[N:13][N:12]=2)[CH2:38][CH2:37]1

Participants

6

Reactant 4

HCID 81503Bromomethylcyclopropane3×HCID 81531DiisopropylethylamineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 167225873-Methoxy-4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-phenylamine

Product 1

HCID 16722640HCID 16722640, compoundYield 10.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3-methoxy-4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-phenylamine (200 mg, 0.57 mmol) in THF (2 mL) was added N,N-diisopropyl ethyl amine (128 μL, 0.75 mmol) and bromomethyl-cyclopropane (61 μL, 0.63 mmol) and the reaction mixture was stirred for 24 h at ambient temperature. After addition of potassium bis(trimethylsilyl)amide (0.91 M in THF, 0.82 mL, 0.75 mmol) stirring was continued for 15 min and further bromomethyl-cyclopropane (78 μL, 0.80 mmol) was added. After stirring for 18 h at ambient temperature further bromomethyl-cyclopropane (0.12 mL, 1.2 mmol) was added and stirring continued for 24 h at this temperature. The reaction mixture was extracted with aqueous sodium carbonate (saturated, 20 mL) and ethyl acetate (20 mL). The aqueous layer was extracted with ethyl acetate (20 mL) and the combined organic layers dried over sodium sulfate. Concentration and then purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=40:40:20 to 0:80:20) afforded the title compound (27 mg, 10%) as a light brown solid. MS: m/e=457.4 [M+H]+.

Workup

  1. stirringstirring
  2. waitwas continued for 15 min
  3. additionwas added
  4. stirringstirring
  5. waitcontinued for 24 h at this temperature
  6. extractionThe reaction mixture was extracted with aqueous sodium carbonate (saturated, 20 mL) and ethyl acetate (20 mL)
  7. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  8. dry with materialthe combined organic layers dried over sodium sulfate
  9. concentrationConcentration
  10. custompurification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=40:40:20 to 0:80:20)

Sources & evidence

ORD record
ord-b55d1c3165154eb4be15984c27befbf0
Source dataset
uspto-grants-2011_06
Patent number
US07956074B2

Reaction notes

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