Potassium bis(trimethylsilyl)amide → HCID 69652406, compound

HRID 2212206Notes

Reaction equation

HRID 2212206 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:11]([O:13][C:14]([CH:16]1[CH2:21][CH:20]([NH:22][C:23]([C:25]2[C:26]([C:31]3[C:36](F)=[CH:35][CH:34]=[CH:33][C:32]=3[Cl:38])=[N:27][O:28][C:29]=2[CH3:30])=[O:24])[CH2:19][N:18]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:17]1)=[O:15])[CH3:12]>CN(C=O)C>[CH2:11]([O:13][C:14]([CH:16]1[CH2:21][CH:20]([N:22]2[C:36]3[CH:35]=[CH:34][CH:33]=[C:32]([Cl:38])[C:31]=3[C:26]3=[N:27][O:28][C:29]([CH3:30])=[C:25]3[C:23]2=[O:24])[CH2:19][N:18]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:17]1)=[O:15])[CH3:12]

Participants

4

Reactant 2

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 69652394HCID 69652394, compound

Product 1

HCID 69652406HCID 69652406, compoundYield 36.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add KHMDS (1.6 mL, 0.80 mmol, 0.5 M in toluene) to a solution of 5-{[3-(2-chloro-6-fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-amino}-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (0.27 g, 0.53 mmol) in DMF (10 mL). After 5 min, quench with water and concentrate to dryness. Dissolve in 20% iPrOH/CHCl3. Wash 2× with sat. aq NaHCO3, wash 2× with brine, dry over Na2SO4, filter, and concentrate to dryness. Purify by radial chromatography using EtOAc/hexanes as eluant and concentrate to dryness to afford the title compound (94 mg, 35%) as a colorless oil as a mixture of cis isomers. MS(IS) 490.1 (M+); HPLC (100% EtOH on a Chiralpak AD (0.46×25 cm) 1.0 mL/min flow; 20 μL Inj. Vol.; 225 nM) Rt=5.688 min (66.3%), 6.462 min (22.9%).

Workup

  1. customquench with water
  2. concentrationconcentrate to dryness
  3. dissolutionDissolve in 20% iPrOH/CHCl3
  4. washWash 2× with sat. aq NaHCO3
  5. washwash 2× with brine
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate to dryness
  9. customPurify by radial chromatography
  10. concentrationconcentrate to dryness

Sources & evidence

ORD record
ord-0d49273e00ff48ab82f6daf22475c0b6
Source dataset
uspto-grants-2006_09
Patent number
US07101891B2

Reaction notes

Loading…