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

HRID 2111719Notes

Reaction equation

HRID 2111719 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-a7ebc92bd56a471ea7463cebfbb7914e
Source dataset
uspto-grants-2009_04
Patent number
US07521445B2

Reaction notes

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