Lithium Hexamethyldisilazide → HCID 54721819, compound

HRID 1436883Notes

Reaction equation

HRID 1436883 reaction equation
[CH:1]1([CH2:4][N:5]([C:24](=[O:30])[C:25]([O:27]CC)=O)[C:6]([CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:11](=[O:23])[CH2:10]2)([CH3:8])[CH3:7])[CH2:3][CH2:2]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>CN(C=O)C>[CH:1]1([CH2:4][N:5]2[C:24](=[O:30])[C:25]([OH:27])=[C:10]3[CH:9]([CH2:14][CH2:13][N:12]([CH2:15][C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[C:11]3=[O:23])[C:6]2([CH3:8])[CH3:7])[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 2733832Lithium HexamethyldisilazideHCID 86620632HCID 86620632, compound

Product 1

HCID 54721819HCID 54721819, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled solution (0° C.) of ethyl ((cyclopropylmethyl){1-[1-(4-fluorobenzyl)-2-oxopiperidin-4-yl]-1-methylethyl}amino)(oxo)acetate (1.56 g, 3.73 mmol) in DMF (15 mL) was added LiHMDS (1M in THF, 5.59 mL, 5.59 mmol) dropwise over 1 min. After stirring for 3 hours, the product mixture was concentrated under vacuum and purified using reverse phase HPLC on C18 stationary phase eluting with a gradient of 5%-95% acetonitrile (0.1% TFA) in H2O (0.1% TFA) to afford the title compound as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.26 (m, 2H), 7.04 (t, J=8.6 Hz, 2H), 4.61 (s, 2H), 3.41 (d, J=6.8 Hz, 2H), 3.32 (d, J=2.8 Hz, 1H), 3.31 (s, 1H), 2.87 (dd, J=13.2; 4.2 Hz, 2H), 1.93 (m, 1H), 1.65 (m, 1H), 1.44 (s, 3H), 1.21 (s, 3H), 1.02 (m, 1H), 0.47 (m, 3H), 0.36 (m, 1H) ppm. ES MS M+1=373.

Workup

  1. concentrationthe product mixture was concentrated under vacuum
  2. custompurified
  3. washeluting with a gradient of 5%-95% acetonitrile (0.1% TFA) in H2O (0.1% TFA)

Sources & evidence

ORD record
ord-604bc9a10ac44fd0a9b0f5ef33d9fb62
Source dataset
uspto-grants-2009_11
Patent number
US07619086B2

Reaction notes

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