Dimethylformamide → 2-Propen-1-yl (5-(6-isoquinolinyl)-3-isoxazolyl)((2S)-2-methyl-3-(4-(trifluoromethyl)phenyl)propyl)carbamate

HRID 598844Notes

Reaction equation

HRID 598844 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[O:15][N:14]=[C:13]([NH:16][C:17](=[O:22])[O:18][CH2:19][CH:20]=[CH2:21])[CH:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[H-].[Na+].[F:25][C:26]([F:49])([F:48])[C:27]1[CH:47]=[CH:46][C:30]([CH2:31][C@H:32]2[CH2:36]OS(=O)(=O)N2C(OC(C)(C)C)=O)=[CH:29][CH:28]=1.[OH-].[Na+].[CH3:52]N(C=O)C>>[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[O:15][N:14]=[C:13]([N:16]([CH2:52][C@@H:32]([CH3:36])[CH2:31][C:30]4[CH:29]=[CH:28][C:27]([C:26]([F:25])([F:48])[F:49])=[CH:47][CH:46]=4)[C:17](=[O:22])[O:18][CH2:19][CH:20]=[CH2:21])[CH:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 57634052tert-Butyl (4S)-4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxideHCID 67062576Allyl 5-(isoquinolin-6-yl)isoxazol-3-ylcarbamate

Product 1

HCID 579505482-Propen-1-yl (5-(6-isoquinolinyl)-3-isoxazolyl)((2S)-2-methyl-3-(4-(trifluoromethyl)phenyl)propyl)carbamateYield 51%

Procedure

To a solution of allyl 5-(isoquinolin-6-yl)isoxazol-3-ylcarbamate (0.030 g, 0.10 mmol) in 1 mL of DMF was added sodium hydride (0.0049 g, 0.20 mmol). After 15 minutes, (S)-tert-butyl 4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate-2,2-dioxide (0.077 g, 0.20 mmol) (prepared as shown in Scheme 1) was added. The mixture was stirred for 30 minutes. The solvent was removed under reduced pressure and the residue was taken up in 5 mL of EtOAc. 5 mL of 10% aq. HCl was then added and the mixture was stirred for 1 hour. A precipitate formed during this period. 10 mL of 5% aqueous NaOH was then added to solubilize the precipitate and the biphasic mixture was partitioned in a separatory funnel. The aqueous portion was extracted three times with 5 mL of EtOAc. The combined organic extracts were washed with 5 mL of brine and dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (10% to 50% EtOAc/hexanes) afforded the desired adduct (0.031 g, 51% yield) as a white solid.

Workup

  1. customThe solvent was removed under reduced pressure
  2. addition5 mL of 10% aq. HCl was then added
  3. stirringthe mixture was stirred for 1 hour
  4. customA precipitate formed during this period
  5. customthe biphasic mixture was partitioned in a separatory funnel
  6. extractionThe aqueous portion was extracted three times with 5 mL of EtOAc
  7. washThe combined organic extracts were washed with 5 mL of brine
  8. dry with materialdried over MgSO4
  9. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-33b1ef31c8ae43698d2d0a9be3fc9b6c
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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