Dichloromethane → Benzyl N-(tert-butoxycarbonyl)-4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-L-phenylalaninate

HRID 724704Notes

Reaction equation

HRID 724704 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:20][C:21]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=1)[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:36]([N:40]1[C:44](=[O:45])[CH:43]=[C:42](Cl)[S:41]1(=[O:48])=[O:47])([CH3:39])([CH3:38])[CH3:37].ClCCl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:10]([O:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:11])[CH2:20][C:21]1[CH:22]=[CH:23][C:24]([C:42]2[S:41](=[O:47])(=[O:48])[N:40]([C:36]([CH3:38])([CH3:37])[CH3:39])[C:44](=[O:45])[CH:43]=2)=[CH:25][CH:26]=1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 218786382-Tert-butyl-5-chloro-2,3-dihydro-1lambda6,2-thiazole-1,1,3-trioneHCID 58746674benzyl(2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate

Product 1

HCID 11720867Benzyl N-(tert-butoxycarbonyl)-4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-L-phenylalaninateYield 37.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of benzyl(2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate (3.33 g, 6.92 mmol), 2-tert-Butyl-5-chloro-1,1-dioxo-1,2-dihydro-1λ6-isothiazol-3-one (1.86 g, 8.31 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.68 g, 0.83 mmol), and potassium carbonate (4.78 g, 0.0346 mol) in 1,4-dioxane (25 mL) were added to a flask with a reflux condenser. The reaction atmosphere was evacuated and purged four times with dry nitrogen. The reaction was heated at 80° C. overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. ethyl acetate extracts were washed with saturated brine and dried over anhyd. sodium sulfate, filtered and concentrated to an oil. The crude was eluted with 10%–30% ethyl acetate in hexanes to give the product (1.4 g, 37%). LCMS found for C28H35N2O7S (M+H)+: m/z=543.

Workup

  1. customThe reaction atmosphere
  2. customwas evacuated
  3. custompurged four times with dry nitrogen
  4. additionThe reaction mixture was diluted with water
  5. extractionextracted with ethyl acetate
  6. washethyl acetate extracts were washed with saturated brine
  7. customdried over anhyd
  8. filtrationsodium sulfate, filtered
  9. concentrationconcentrated to an oil
  10. washThe crude was eluted with 10%–30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6c28f0cff75747ce972d1b25bbb695a8
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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