HCID 67153303, compound → 2-(3-formyl-benzyl)-1,1-dioxo-1lambda6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide

HRID 1879473Notes

Reaction equation

HRID 1879473 reaction equation
[CH3:1][C@@H:2]1[C@@H:7]([NH:8][C:9]([CH:11]2[CH2:15][CH2:14][S:13](=[O:17])(=[O:16])[N:12]2[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]#N)[CH:20]=2)=[O:10])[CH2:6][C@H:5]2[CH2:27][C@@H:3]1[C:4]2([CH3:29])[CH3:28].O.P(P([O-])([O-])=O)([O-])([O-])=[O:32].[Na+].[Na+].[Na+].[Na+]>N1C=CC=CC=1CC(O)=O.O.[Ni]>[CH3:1][C@@H:2]1[C@@H:7]([NH:8][C:9]([CH:11]2[CH2:15][CH2:14][S:13](=[O:17])(=[O:16])[N:12]2[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]=[O:32])[CH:20]=2)=[O:10])[CH2:6][C@H:5]2[CH2:27][C@@H:3]1[C:4]2([CH3:29])[CH3:28]

Participants

5

Reactant 2

HCID 67153303HCID 67153303, compoundHCID 131730070HCID 131730070, compound

Product 1

HCID 872885452-(3-formyl-benzyl)-1,1-dioxo-1lambda6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amideYield 49.8%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 69477857Pyridine-acetic acid waterSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2-(3-cyano-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide (0.200 g, 0.48 mmol) in a mixture of pyridine-acetic acid-water (2:1:1; 7.2 mL) was added sodium hypophosphate hydrate (0.400 g, 3.77 mmol) at room temperature. The reaction mixture was cooled to 0° C. and Raney Nickel (0.200 g) was added under an argon atmosphere. After stirring at 0° C. for 10 min, the temperature was raised to 40-45° C. and the reaction mixture was stirred for an additional 2.5 h at the same temperature (with monitoring by silica TLC). The reaction mixture was cooled, filtered through a pad of celite and the residue was washed with methanol (5 mL). The combined filtrates were concentrated to provide the crude material, which was purified by silica gel column chromatography (100-200 mesh) using a gradient of 50-60% ethyl acetate/hexanes to give 2-(3-formyl-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide (0.100 g, 49%).

Workup

  1. temperaturethe temperature was raised to 40-45° C.
  2. stirringthe reaction mixture was stirred for an additional 2.5 h at the same temperature (with monitoring by silica TLC)
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered through a pad of celite
  5. washthe residue was washed with methanol (5 mL)
  6. concentrationThe combined filtrates were concentrated
  7. customto provide the crude material, which
  8. customwas purified by silica gel column chromatography (100-200 mesh)

Sources & evidence

ORD record
ord-de4527d00b954805b749579f14c08f31
Source dataset
uspto-grants-2012_11
Patent number
US08314250B2

Reaction notes

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