Lithium Hexamethyldisilazide → 2-(4-Tert-butoxycarbonylamino-cyclohexyl)-3-(6-methoxy-quinolin-4-yl)-3-oxo-propionic acid methyl ester

HRID 723513Notes

Reaction equation

HRID 723513 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7][CH2:6]1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].C[O:31][C:32]([C:34]1[C:43]2[C:38](=[CH:39][CH:40]=[C:41]([O:44][CH3:45])[CH:42]=2)[N:37]=[CH:36][CH:35]=1)=O>O1CCCC1>[CH3:1][O:2][C:3](=[O:19])[CH:4]([CH:5]1[CH2:6][CH2:7][CH:8]([NH:11][C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])[CH2:9][CH2:10]1)[C:32]([C:34]1[C:43]2[C:38](=[CH:39][CH:40]=[C:41]([O:44][CH3:45])[CH:42]=2)[N:37]=[CH:36][CH:35]=1)=[O:31]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 141101324-Quinolinecarboxylic acid, 6-methoxy-, methyl esterHCID 261928274-N-BOC-cyclohexyacetic acid methyl ester

Product 1

HCID 693777782-(4-Tert-butoxycarbonylamino-cyclohexyl)-3-(6-methoxy-quinolin-4-yl)-3-oxo-propionic acid methyl esterYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

(4-Tert-Butoxycarbonylamino-cyclohexyl)-acetic acid methyl ester (1.00 g, 3.69 mmol) was dissolved in tetrahydrofuran (20 mL) and cooled to −78° C. To the solution lithium hexamethyldisilazide in tetrahydrofuran (1M, 11.0 mL, 11.0 mmol) was added dropwise. The reaction mixture was stirred for 20 minutes at −78° C. and then 6-methoxy-quinoline-4-carboxylic acid methyl ester (1.60 g, 7.38 mmol) was added as a solution in tetrahydrofuran (10 mL). The mixture was allowed to warm to room temperature and stirred for 12 hours. The reaction was quenched by the addition of water (2 mL), the solvent removed in vacuo and the residue partitioned between ethyl acetate (2×100 mL) and water (20 mL). The pH of the aqueous phase was adjusted to 10 to obtain the maximum degree of extracted material into the organic phases. The organic phases were combined, dried over magnesium sulfate and the volatiles removed under suction. The resulting residue was purified by column chromatography on silica gel using an ethyl acetate and hexane solvent gradient to provide the desired compound as a colourless oil (190 mg, 12%).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 12 hours
  3. customThe reaction was quenched by the addition of water (2 mL)
  4. customthe solvent removed in vacuo
  5. customthe residue partitioned between ethyl acetate (2×100 mL) and water (20 mL)
  6. customto obtain the maximum degree of extracted material into the organic phases
  7. dry with materialdried over magnesium sulfate
  8. customthe volatiles removed under suction
  9. customThe resulting residue was purified by column chromatography on silica gel using an ethyl acetate and hexane solvent gradient

Sources & evidence

ORD record
ord-4b4ae657ba104eaa8c4f2e6f5d96ba51
Source dataset
uspto-grants-2006_11
Patent number
US07141564B2

Reaction notes

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