Lithium Hexamethyldisilazide → HCID 178500885, compound

HRID 1666099Notes

Reaction equation

HRID 1666099 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH2:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7][CH2:6]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:30][O:31][C:32]1[N:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[N:38]=[CH:37][CH:36]=[C:35]2[CH:42]=[O:43]>C1COCC1>[CH3:1][O:2][C:3](=[O:19])[CH:4]([C@H:5]1[CH2:6][CH2:7][C@H:8]([NH:11][C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])[CH2:9][CH2:10]1)[CH:42]([OH:43])[C:35]1[C:34]2[C:39](=[CH:40][CH:41]=[C:32]([O:31][CH3:30])[N:33]=2)[N:38]=[CH:37][CH:36]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 665231381,5-Naphthyridine-4-carboxaldehyde, 6-methoxy-HCID 178500703HCID 178500703, compound

Product 1

HCID 178500885HCID 178500885, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of trans-(4-tert-butoxycarbonylaminocyclohexyl)-acetic acid methyl ester (1.80 g, 6.63 mmol; prepared according to WO 2000/024717) in THF (20 mL) cooled to −78° C. was added LiHMDS (1M in THF, 17.1 mL) dropwise over 10 minutes. The resulting solution was stirred for 1.5 h in a dry-ice bath letting the temperature settle at −40° C. The reaction was cooled again to −78° C. and 6-methoxy-[1,5]naphthyridine-4-carbaldehyde (3.35 g, 17.82 mmol; prepared according to WO 2006/032466) was added quickly as a solid (2 mL THF were also added for rinse) and stirring was continued for 1.75 h at −78° C. Aq. NH4Cl (50 mL) and EA (50 mL) were added. The two layers were separated and the aq. layer was extracted once with EA (50 mL). The combined org. layers were washed with brine (60 mL), dried over Na2SO4, filtered and concentrated to dryness. The residue was chromatographed (Hept-EA 1-1 to 1-4) to give the title compound as a pale yellow solid (2.68 g, 88% yield). The compound was obtained as a 1-1 mixture of (syn,anti)-isomers, contaminated by 10% of the starting aldehyde.

Workup

  1. customsettle at −40° C
  2. additionwere also added
  3. washfor rinse) and
  4. stirringstirring
  5. waitwas continued for 1.75 h at −78° C
  6. additionAq. NH4Cl (50 mL) and EA (50 mL) were added
  7. customThe two layers were separated
  8. extractionthe aq. layer was extracted once with EA (50 mL)
  9. washlayers were washed with brine (60 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated to dryness
  13. customThe residue was chromatographed (Hept-EA 1-1 to 1-4)

Sources & evidence

ORD record
ord-c8d491cbf90f483180eb47b59b5c8f79
Source dataset
uspto-grants-2011_10
Patent number
US08044044B2

Reaction notes

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