Cesium carbonate → 4-(5-Methoxymethyl-thieno[2,3-d]isoxazol-3-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 456531Notes

Reaction equation

HRID 456531 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]([C:23]2[S:24][C:25]([CH2:29][O:30][CH3:31])=[CH:26][C:27]=2Br)=[N:21][OH:22])[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]>COCCO.[Cu](I)I>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[C:23]3[S:24][C:25]([CH2:29][O:30][CH3:31])=[CH:26][C:27]=3[O:22][N:21]=2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]

Participants

5

Reactant 2

HCID 10796Cesium carbonateHCID 724345774-[1-(3-Bromo-5-methoxymethyl-thiophen-2-yl)-1-hydroxyimino-methyl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 588176364-(5-Methoxymethyl-thieno[2,3-d]isoxazol-3-yl)-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 80192-MethoxyethanolSolvent

Procedure

Add cesium carbonate (1.13 g, 3.46 mmol, 1.50 equivalents) and copper iodide (44 mg, 0.23 mmol, 0.10 equivalents) to a stirred solution of 4-[1-(3-bromo-5-methoxymethyl-thiophen-2-yl)-1-hydroxyimino-methyl]-piperidine-1-carboxylic acid tert-butyl ester (1.00 g, 2.31 mmol, 1.00 equivalents) in 2-methoxy ethanol (23.30 mL). Stir the resulting mixture at room temperature overnight or up to 3 days and filter through celite. Evaporate the filtrate, partition the residue between ethyl acetate (70 mL) and water (23 mL) and separate. Extract the aqueous layer with ethyl acetate (3×70 mL), combine the organic layers, dry over magnesium sulfate, filter and evaporate. Purify the residue via flash column chromatography eluting with a mixture of hexane: ethyl acetate (4:1) to yield the desired product as a yellow oil. LC/MS (ESI), m/e 375 (MNa+), retention time 1.98 minutes. Condition II.

Workup

  1. waitup to 3 days
  2. filtrationfilter through celite
  3. customEvaporate the filtrate
  4. custompartition the residue between ethyl acetate (70 mL) and water (23 mL)
  5. customseparate
  6. extractionExtract the aqueous layer with ethyl acetate (3×70 mL)
  7. dry with materialdry over magnesium sulfate
  8. filtrationfilter
  9. customevaporate
  10. customPurify the residue via flash column chromatography
  11. washeluting with a mixture of hexane: ethyl acetate (4:1)

Sources & evidence

ORD record
ord-8085a0cf148148f5af582df07c2a6eab
Source dataset
uspto-grants-2007_03
Patent number
US07186724B2

Reaction notes

Loading…