Saccharin → (2r)-t-Butoxycarbonylamino-5-(1,1,3-trioxo-2,3-dihydrobenzoisothiazol-2-yl)pentanoic acid t-butyl ester

HRID 2187989Notes

Reaction equation

HRID 2187989 reaction equation
[H-].[Na+].[S:3]1([C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:7](=[O:8])[NH:6]1)(=[O:5])=[O:4].[C:15]([O:19][C:20](=[O:34])[C@H:21]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22][CH2:23][CH2:24]I)([CH3:18])([CH3:17])[CH3:16]>CN(C=O)C.C1OCCOCCOCCOCCOCCOC1>[C:15]([O:19][C:20](=[O:34])[C@H:21]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22][CH2:23][CH2:24][N:6]1[C:7](=[O:8])[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=2[S:3]1(=[O:4])=[O:5])([CH3:16])([CH3:17])[CH3:18]

Participants

6

Reactant 3

HCID 5143SaccharinHCID 24758Sodium hydrideHCID 15479355N-Boc-5-Iodo-D-norvaline tert-butyl ester

Product 1

HCID 69287698(2r)-t-Butoxycarbonylamino-5-(1,1,3-trioxo-2,3-dihydrobenzoisothiazol-2-yl)pentanoic acid t-butyl esterYield 63%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (0.311 g, 7.78 mmol) was added to a solution of saccharin (1.73 g, 9.44 mmol) and 18-crown-6 (0.025 g) in 10 mL of DMF. After stirring at RT for 30 min, (2R)-(t-butyloxycarbonylamino)-5-iodopentanoic acid t-butyl ester (2.78 g, 6.96 mmol) in 10 mL of DMF was added, and the solution was stirred at RT for 30 min, then at 60° C. for 6 h. The solvent was removed under reduced pressure, and the residue was partitioned between ethyl acetate and 0.05M aqueous HCl. The organic phase was washed with water and brine, dried over MgSO4 and concentrated. The crude material was purified by silica gel chromatography (hexane/ethyl acetate=4/1˜3/1) to give the title compound (1.98 g, 63% yield): NMR (400 MHz, CDCl3) 1.44 (s, 9H), 1.46 (s, 9H), 1.68-1.96 (m, 4H), 3.81 (t, 2H, J=7.0 Hz), 4.19-4.29 (m, 1H), 5.09 (br d, 1H, J=7.9 Hz), 7.82-7.93 (m, 3H), 806 (d, 1H, J=7.3 Hz).

Workup

  1. stirringthe solution was stirred at RT for 30 min
  2. waitat 60° C. for 6 h
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was partitioned between ethyl acetate and 0.05M aqueous HCl
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude material was purified by silica gel chromatography (hexane/ethyl acetate=4/1˜3/1)

Sources & evidence

ORD record
ord-96195b17e5cb490194ea5783cdf1f8f0
Source dataset
uspto-grants-2002_06
Patent number
US06410580B1

Reaction notes

Loading…