Water → HCID 67181383, compound

HRID 1801471Notes

Reaction equation

HRID 1801471 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:11]([O:13][C:14](=[O:25])[CH2:15][CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH3:12].Br[CH2:27][C:28]1[C:29]([F:40])=[CH:30][N:31]=[C:32]2[C:37]=1[N:36]=[C:35]([O:38][CH3:39])[CH:34]=[CH:33]2.O>C1COCC1.CC(=O)OCC>[CH2:11]([O:13][C:14](=[O:25])[CH:15]([CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[C:35]([O:38][CH3:39])[N:36]=2)[N:31]=[CH:30][C:29]=1[F:40])[CH3:12]

Participants

7

Reactant 4

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 15933116Ethyl 3-{[(tert-butoxy)carbonyl]amino}propanoateHCID 67223878HCID 67223878, compound

Product 1

HCID 67181383HCID 67181383, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of LiHMDS (1M, 17 mL, 2.2 eq.), cooled to −78° C., was added dropwise a solution of 3-tert-butoxycarbonylamino-propionic acid ethyl ester (1.70 g, 7.82 mmol, prepared according to Tetrahedron Lett. (2003), 44, 2807-2811) in THF (20 mL). The solution was stirred at the same temperature for 90 min. A solution of 8-bromomethyl-7-fluoro-2-methoxy-[1,5]naphthyridine (2.12 g, 1 eq., prepared according to WO 2008/078305) in THF (10 mL) was quickly added and the reaction proceeded 2 h, keeping the internal temperature below −50° C. Water (100 mL) and EA (200 mL) were added. The two layers were decanted and the aq. layer was extracted with EA. The combined org. layers were washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was chromatographed (Hept-EA 2-1) to afford the title intermediate as a yellow oil (2.38 g, 75% yield).

Workup

  1. waitthe reaction proceeded 2 h
  2. customthe internal temperature below −50° C
  3. customThe two layers were decanted
  4. extractionthe aq. layer was extracted with EA
  5. washlayers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe residue was chromatographed (Hept-EA 2-1)

Sources & evidence

ORD record
ord-7664b219bb7d48a3a80515b374aa490c
Source dataset
uspto-grants-2013_01
Patent number
US08349828B2

Reaction notes

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