Isopropylamine → HCID 49804754, compound

HRID 1807491Notes

Reaction equation

HRID 1807491 reaction equation
C[Al](C)C.[CH:5]([NH2:8])([CH3:7])[CH3:6].C[O:10][C:11](=O)[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:21]([CH2:26][CH2:27][C:28]([F:31])([F:30])[F:29])=[N:22][O:23][C:24]=2[CH3:25])=[N:14][CH:13]=1>C1(C)C=CC=CC=1.O1CCOCC1>[CH:5]([O:23][CH:24]([CH3:25])[CH3:20])([CH3:7])[CH3:6].[CH:5]([NH:8][C:11](=[O:10])[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:21]([CH2:26][CH2:27][C:28]([F:31])([F:29])[F:30])=[N:22][O:23][C:24]=2[CH3:25])=[N:14][CH:13]=1)([CH3:7])[CH3:6]

Participants

7

Reactant 3

HCID 6363IsopropylamineHCID 16682925TrimethylaluminumHCID 66643649HCID 66643649, compound

Product 2

HCID 7914Diisopropyl EtherHCID 49804754HCID 49804754, compoundYield 128%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

Trimethylaluminium (1.22 mL of a 2 M solution in toluene, 2.44 mmol) was added dropwise to a stirred solution of isopropylamine (144 mg, 2.46 mmol) in dioxane (4 mL) at room temperature and under argon. After 1 h, a solution of 6-[5-methyl-3-(3,3,3-trifluoro-propyl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (210 mg, 0.61 mmol) in dioxane (4 mL) was added and the reaction mixture warmed to 90° C. After 10 h the reaction mixture was cooled and poured onto ice/water. The resultant mixture was extracted with ethylacetate then the combined extracts were washed with Seignette salt solution. The organic phase was dried, filtered and evaporated then purified by chromatography (silica, 0 to 60% ethyl acetate in heptane) then trituration with diisopropyl ether to give the title compound (145 mg, 64%) as a white solid. MS: m/e=372.3 [M+H]+.

Workup

  1. temperatureAfter 10 h the reaction mixture was cooled
  2. additionpoured onto ice/water
  3. extractionThe resultant mixture was extracted with ethylacetate
  4. washthe combined extracts were washed with Seignette salt solution
  5. customThe organic phase was dried
  6. filtrationfiltered
  7. customevaporated
  8. customthen purified by chromatography (silica, 0 to 60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-d7fa8928b6874ca9a5d258a9982d463d
Source dataset
uspto-grants-2013_01
Patent number
US08357703B2

Reaction notes

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