Triethylamine → HCID 69652394, compound

HRID 2212187Notes

Reaction equation

HRID 2212187 reaction equation
[F-].[CH2:2]([N+](CCCC)(CCCC)CCCC)CCC.[CH2:19]([O:21][C:22]([CH:24]1[CH2:29][CH:28]([NH:30][C:31]([O:33]CC[Si](C)(C)C)=O)[CH2:27][N:26]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:25]1)=[O:23])[CH3:20].CCN(CC)CC.[Cl:54][C:55]1[CH:60]=[CH:59][CH:58]=[C:57]([F:61])[C:56]=1[C:62]1(C)[C:66](C(Cl)=O)=[CH:65][O:64][NH:63]1>C1COCC1.CN(C1C=CN=CC=1)C.C(Cl)Cl.C(Cl)(Cl)Cl>[CH2:19]([O:21][C:22]([CH:24]1[CH2:29][CH:28]([NH:30][C:31]([C:66]2[C:62]([C:56]3[C:57]([F:61])=[CH:58][CH:59]=[CH:60][C:55]=3[Cl:54])=[N:63][O:64][C:65]=2[CH3:2])=[O:33])[CH2:27][N:26]([C:40]([O:42][C:43]([CH3:44])([CH3:45])[CH3:46])=[O:41])[CH2:25]1)=[O:23])[CH3:20]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 69652396HCID 69652396, compoundHCID 86592847HCID 86592847, compound

Product 1

HCID 69652394HCID 69652394, compoundYield 46.3%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add resin-bound tetrabutylammonium fluoride (TBAF) (22 g, 22.0 mmol, 1.6 mmol F/gram) to a solution of 5-(2-trimethylsilanyl-ethoxycarbonylamino)-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (4.63 g, 11.0 mmol) in THF (150 mL). Reflux 48 H, cool to room temperature and concentrate to dryness. Dissolve in CHCl3. Wash 2× sat. aq NaHCO3, wash 2× brine, dry over Na2SO4, filter, and concentrate to dryness. Add Et3N (4.6 mL, 33.0 mmol) and DMAP (5 mg, cat.) to a solution of the residue (3.0 g, 11.0 mmol) in CH2Cl2 (100 mL). Add 3-(2-chloro-6-fluoro-phenyl)-3-methyl-isoxazole-4 carbonyl chloride (4.3 g, 15.4 mmol, Great Lakes Chemical) and stir overnight at room temperature. Add CHCl3. Wash 2× with sat. aq NaHCO3, wash 2× with brine, dry over Na2SO4, filter and concentrate to dryness. Purify by column chromatography using EtOAc/hexanes as eluant and concentrate to dryness to yield the title compound (2.6 g, 46%) as a yellow foam as a mixture of cis isomers. MS(IS) 510.2 (M+); Anal. Calc'd for C24H29ClFN3O4.0.05CHCl3: C, 55.99; H, 5.68; N, 8.14. Found: C, 55.91; H, 5.72; N, 8.03.

Workup

  1. temperatureReflux 48 H
  2. concentrationconcentrate to dryness
  3. dissolutionDissolve in CHCl3
  4. washWash 2× sat. aq NaHCO3
  5. washwash 2× brine
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate to dryness
  9. washWash 2× with sat. aq NaHCO3
  10. washwash 2× with brine
  11. dry with materialdry over Na2SO4
  12. filtrationfilter
  13. concentrationconcentrate to dryness
  14. customPurify by column chromatography
  15. concentrationconcentrate to dryness

Sources & evidence

ORD record
ord-961915e3958e4e38a51700e403e58dd0
Source dataset
uspto-grants-2006_09
Patent number
US07101891B2

Reaction notes

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