Sparteine → 3-[(2R,3S)-2-{[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]carbonyl}-5-(3',5'-difluorobiphenyl-4-yl)-3-hydroxypentyl]-1,2,3-benzotriazin-4(3H)-one

HRID 2410461Notes

Reaction equation

HRID 2410461 reaction equation
[CH2:1]([C@H:8]1[CH2:12][S:11][C:10](=[O:13])[N:9]1[C:14](=[O:28])[CH2:15][CH2:16][N:17]1[C:22](=[O:23])[C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]=[N:18]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C[C@H]2N(C[C@H]3[C@@H]4CCCCN4C[C@@H]2C3)CC1.[F:46][C:47]1[CH:48]=[C:49]([C:54]2[CH:59]=[CH:58][C:57]([CH2:60][CH2:61][CH:62]=[O:63])=[CH:56][CH:55]=2)[CH:50]=[C:51]([F:53])[CH:52]=1>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[CH2:1]([C@H:8]1[CH2:12][S:11][C:10](=[O:13])[N:9]1[C:14]([C@@H:15]([C@@H:62]([OH:63])[CH2:61][CH2:60][C:57]1[CH:58]=[CH:59][C:54]([C:49]2[CH:48]=[C:47]([F:46])[CH:52]=[C:51]([F:53])[CH:50]=2)=[CH:55][CH:56]=1)[CH2:16][N:17]1[C:22](=[O:23])[C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]=[N:18]1)=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 644020SparteineHCID 671829553-{3-[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-3-oxopropyl}-1,2,3-benzotriazin-4(3H)-oneHCID 867009823-(3',5'-Difluorobiphenyl-4-yl)propanal

Product 1

HCID 671823083-[(2R,3S)-2-{[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]carbonyl}-5-(3',5'-difluorobiphenyl-4-yl)-3-hydroxypentyl]-1,2,3-benzotriazin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

In a flame-dried flask, 3-{3-[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-3-oxopropyl}-1,2,3-benzotriazin-4(3H)-one (0.25 g) was taken up in dichloromethane (10 mL) and cooled to 0° C. Titanium tetrachloride (0.76 mL, 1 M solution) was added drop-wise and the reaction mixture was stirred for 10 to 15 minutes. (−)-Sparteine (0.36 mL) was added slowly to the reaction mixture and stirred at 0° C. for 20 minutes. A solution of the compound obtained from step e above (0.187 g) in dichloromethane (10 mL) was added slowly and stirring was continued at 0° C. After 3 hours, the reaction was quenched with the drop-wise addition of saturated ammonium chloride solution, and dichloromethane was added. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulphate, and concentrated under reduced pressure. The crude product thus obtained was purified by silica gel flash column chromatography using 30% ethyl acetate in hexane as eluant to afford the title compound (0.24 g).

Workup

  1. stirringstirred at 0° C. for 20 minutes
  2. stirringstirring
  3. customwas continued at 0° C
  4. waitAfter 3 hours
  5. customthe reaction was quenched with the drop-wise addition of saturated ammonium chloride solution, and dichloromethane
  6. additionwas added
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with dichloromethane
  9. washThe organic layer was washed with brine
  10. dry with materialdried over anhydrous sodium sulphate
  11. concentrationconcentrated under reduced pressure
  12. customThe crude product thus obtained
  13. customwas purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-c75c10b035bf4118b217d7015565894f
Source dataset
uspto-grants-2014_08
Patent number
US08816073B2

Reaction notes

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