Isopropylamine → HCID 46928465, compound

HRID 1514667Notes

Reaction equation

HRID 1514667 reaction equation
C[Al](C)C.[CH:5]([NH2:8])([CH3:7])[CH3:6].CO[C:11](=[O:40])[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:21]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[N:22][O:23][C:24]=2[C:25](C)(C)[O:26][SiH2]C(C)(C)C)=[N:14][CH:13]=1.C(OCC)(=O)C>CCCCCC.O1CCOCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>[OH:26][CH2:25][C:24]1[O:23][N:22]=[C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:20]=1[CH2:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([C:11]([NH:8][CH:5]([CH3:7])[CH3:6])=[O:40])=[CH:13][N:14]=1

Participants

9

Reactant 4

HCID 6363IsopropylamineHCID 8857Ethyl AcetateHCID 16682925TrimethylaluminumHCID 131729833HCID 131729833, compound

Product 1

HCID 46928465HCID 46928465, compoundYield 18.6%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 312751,4-DioxaneSolvent2×HCID 2724141Tetrabutylammonium FluorideSolvent

Procedure

Trimethylaluminum (4.4 mL of a 2M solution in hexane, 8.8 mmol) was slowly added to a solution of isopropylamine (0.76 mL, 8.9 mmol) in dioxane (7.5 mL) and stirred at room temperature for 1 h. Then a solution of 6-[5-(tert-butyl-dimethyl-silanyloxymethyl)-3-phenyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (1.0 g, 2.2 mmol) in dioxane (7.5 mL) was added dropwise. The mixture was stirred at 90° C. for 2 h. After cooling to room temperature and extractive workup (ethyl acetate/aqueous saturated Seignette salt solution) the organic phase was dried (Na2SO4) and filtered over a silica pad. The solvent was evaporated to furnish an intermediate which was dissolved in a tetrabutylammonium fluoride solution (2 mL of a 1M in THF). After 1 h the reaction mixture was extractively worked up (ethyl acetate/aqueous saturated citric acid). The organic phase was dried over sodium sulfate, filtred and concentrated and then purified by HPLC (Chiralpak AD, heptane/ethanol) to afford the title compound as a colorless oil (0.15 g, 18%). MS: m/e=368.3 [M+H]+.

Workup

  1. stirringThe mixture was stirred at 90° C. for 2 h
  2. temperatureAfter cooling to room temperature
  3. dry with materialextractive workup (ethyl acetate/aqueous saturated Seignette salt solution) the organic phase was dried (Na2SO4)
  4. filtrationfiltered over a silica pad
  5. customThe solvent was evaporated
  6. customto furnish an intermediate which
  7. waitAfter 1 h the reaction mixture was extractively worked up
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. concentrationconcentrated
  10. custompurified by HPLC (Chiralpak AD, heptane/ethanol)

Sources & evidence

ORD record
ord-97dec0569db141a18ef7c839e9adb468
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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