Lithium Hexamethyldisilazide → HCID 86701199, compound

HRID 2406333Notes

Reaction equation

HRID 2406333 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Br:11][C:12]1[C:13]([CH3:19])=[CH:14][C:15]([Cl:18])=[N:16][CH:17]=1.[C:20]([O:24][C:25]([N:27]1[CH2:36][CH2:35][C:30]2([CH2:33][C:32](=[O:34])[CH2:31]2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]>O1CCCC1>[C:20]([O:24][C:25]([N:27]1[CH2:28][CH2:29][C:30]2([CH2:31][C:32]([CH2:19][C:13]3[C:12]([Br:11])=[CH:17][N:16]=[C:15]([Cl:18])[CH:14]=3)([OH:34])[CH2:33]2)[CH2:35][CH2:36]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27344275-Bromo-2-chloro-4-methylpyridineHCID 11195798Tert-butyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate

Product 1

HCID 86701199HCID 86701199, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

Lithium bis(trimethylsilyl)amide (1.0 mol/L in tetrahydrofuran; 8.0 mL) is added dropwise to 5-bromo-2-chloro-4-picoline (0.81 g) dissolved in tetrahydrofuran (10 mL) at −45° C. under Ar atmosphere. The solution is stirred at −35 to −45° C. for 0.5 h prior to dropwise addition of 2-oxo-7-aza-spiro[3.5]nonane-7-carboxylic acid tert-butyl ester (1.00 g) dissolved in tetrahydrofuran (5 mL). The reaction mixture is stirred at −40° C. for 45 min before the cooling bath is removed. At room temperature the reaction is quenched with aqueous NH4Cl solution and the resulting mixture is extracted with ethyl acetate. The combined extracts are dried (Na2SO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 4:1→1:1) to give the title compound. LC (method 1): tR=1.36 min; Mass spectrum (ESI+): m/z=445 [M+H]+.

Workup

  1. stirringThe reaction mixture is stirred at −40° C. for 45 min before the cooling bath
  2. customis removed
  3. customAt room temperature the reaction is quenched with aqueous NH4Cl solution
  4. extractionthe resulting mixture is extracted with ethyl acetate
  5. dry with materialThe combined extracts are dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 4:1→1:1)

Sources & evidence

ORD record
ord-2edb115d22f048cd9fd3d8c3b13804d8
Source dataset
uspto-grants-2014_08
Patent number
US08809361B2

Reaction notes

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