tert-Butyl acetate → HCID 86596677, compound

HRID 1373585Notes

Reaction equation

HRID 1373585 reaction equation
[C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])(=[O:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:19]([C:22]1[C:23]([NH:29][C:30](=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32])=[N:24][C:25]([Cl:28])=[CH:26][CH:27]=1)(=[O:21])[CH3:20]>C1COCC1>[C:5]([O:4][C:1](=[O:3])[CH2:2][C:19]([C:22]1[C:23]([NH:29][C:30](=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32])=[N:24][C:25]([Cl:28])=[CH:26][CH:27]=1)([OH:21])[CH3:20])([CH3:8])([CH3:7])[CH3:6]

Participants

5

Reactant 3

HCID 10908tert-Butyl acetateHCID 2733832Lithium HexamethyldisilazideHCID 21073954HCID 21073954, compound

Product 1

HCID 86596677HCID 86596677, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A first intermediate compound, 7-Chloro-4-methyl-1H-[1,8]naphthyridin-2-one, was produced as follows: A solution of tert-butyl acetate (0.6 mL, 4.45 mmol) is added dropwise to a solution of lithium bis(trimethylsilyl)amide (1.0 M in THF, 4.2 mL, 4.2 mmol) in THF (5 mL) at −78° C. The yellow solution is stirred for 1 hour and N-(3-acetyl-6-chloro-pyridin-2-yl)-2,2-dimethyl-propionamide (0.503 g, 1.97 mmol) in THF (5 mL) is added dropwise to the mixture. The yellow suspension is stirred at −78° C. for 30 minutes and warmed to RT. The suspension clears to a yellow solution and the mixture is stirred at room temperature for 1.5 hours. The mixture is quenched with water and extracted with CH2Cl2. The organic extracts are washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to a brown liquid. The liquid is purified by column chromatography (2:1 hexanes/ethyl acetate) to afford 3-[6-chloro-2-(2,2-dimethyl-propionylamino)-pyridin-3-yl]-3-hydroxy-butyric acid tert-butyl ester (0.548 g, 75%) as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 10.40 (br s, 1H), 7.37 (d, 1H), 6.98 (d, 1H), 5.61 (s, 1H), 3.03 (d, 1H), 2.67 (d, 1H), 1.56 (s, 3H), 1.45 (s, 9H), 1.32 (s, 9H). MS ES: m/z=370.86, 372.56.

Workup

  1. stirringThe yellow suspension is stirred at −78° C. for 30 minutes
  2. stirringthe mixture is stirred at room temperature for 1.5 hours
  3. customThe mixture is quenched with water
  4. extractionextracted with CH2Cl2
  5. washThe organic extracts are washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to a brown liquid
  9. customThe liquid is purified by column chromatography (2:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-6b45c6c0101b4c80861d3638f9808cc4
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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