N-(tert-Butoxycarbonyl)-4-chloro-L-phenylalanine → (S)-tert-Butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide

HRID 598837Notes

Reaction equation

HRID 598837 reaction equation
FC(F)(F)[C:3]1[CH:23]=[CH:22][C:6]([CH2:7][C@H:8]2[CH2:12][O:11][S:10](=[O:14])(=[O:13])[N:9]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:5][CH:4]=1.[Cl:26]C1C=CC(C[C@H](NC(OC(C)(C)C)=O)C(O)=O)=CC=1.C(OC(N[C@@H](CC1C=CC(C(F)(F)F)=CC=1)C(O)=O)=O)(C)(C)C>>[Cl:26][C:3]1[CH:23]=[CH:22][C:6]([CH2:7][C@H:8]2[CH2:12][O:11][S:10](=[O:14])(=[O:13])[N:9]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:5][CH:4]=1

Participants

4

Reactant 3

HCID 2734499N-(tert-Butoxycarbonyl)-4-chloro-L-phenylalanineHCID 7021025N-((1,1-Dimethylethoxy)carbonyl)-4-(trifluoromethyl)-L-phenylalanineHCID 57634052tert-Butyl (4S)-4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide

Product 1

HCID 86635689(S)-tert-Butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide

Procedure

To a solution of allyl 3-(isoquinolin-6-yl)isoxazol-5-ylcarbamate (0.055 g, 0.19 mmol) in 3 mL of DMF was added cesium carbonate (0.12 g, 0.37 mmol). The mixture was heated to 50° C. (S)-tert-Butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (0.097 g, 0.28 mmol) was added slowly in 0.75 mL of THF. After 30 minutes, the reaction was cooled to room temperature and diluted with 10 mL of EtOAc. 10 mL of 10% HCl was then carefully added. After 30 minutes, the reaction was diluted with 15 mL of 5% aq. NaOH. The biphasic mixture was partitioned and the aqueous portion was extracted twice with 20 mL of EtOAc. The combined organic extracts were washed with twice with 10 mL of water and 15 mL of brine and then dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (20% to 50% EtOAc/hexanes) afforded the desired adduct (0.095 g, 91% yield) as a yellow solid. (S)-tert-Butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide was prepared in a similar manner as that described for (S)-tert-butyl 4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate-2,2-dioxide in Scheme 1, using (S)-3-(4-chlorophenyl)-2-(tert-butoxycarbonylamino)propanoic acid commercially available from 3B Scientific Corporation Product List (Order Number 3B3-011434) instead of (S)-2-(tert-butoxycarbonylamino)-3-(4-(trifluoromethyl)phenyl)propanoic acid.

Sources & evidence

ORD record
ord-e4c02afdc0994d94aa942973ee21d168
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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