Boron trifluoride etherate → 3-(((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)methyl)-1,2,4-thiadiazol-5(4H)-one

HRID 1048299Notes

Reaction equation

HRID 1048299 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[C:11](=[O:26])[C@:10]([CH2:28][C:29](=[N:31]O)[NH2:30])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[C:33](N1C=CN=C1)(N1C=CN=C1)=[S:34].B(F)(F)F.CC[O:51]CC>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[C:11](=[O:26])[C@:10]([CH2:28][C:29]3[NH:30][C:33](=[O:51])[S:34][N:31]=3)([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 802641,1'-ThiocarbonyldiimidazoleHCID 866607192-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)-N'-hydroxyacetimidamide

Product 1

HCID 1363599523-(((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)methyl)-1,2,4-thiadiazol-5(4H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 83 mg (0.17 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)-N′-hydroxyacetimidamide (Example 82, Step C) in THF (4 mL) was added 50 mg (0.28 mmol) of 1,1′-thiocarbonyldiimidazole. The resulting yellow solution was stirred at room temperature for 1 h, and then was quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated. The residue was dissolved in THF (4.5 mL), and 69 μL (0.56 mmol) of boron trifluoride etherate was added via syringe. The resulting light yellow solution was stirred at room temperature for 2.5 h, and then was quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by reversed phase prep. HPLC (Sunfire Prep C18 OBD 10 μm column, gradient elution of 55% MeCN in water to 85% MeCN in water over a 35 min period, where both solvents contain 0.1% TFA) provided the title compound as a white solid.

Workup

  1. customwas quenched with water
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. dissolutionThe residue was dissolved in THF (4.5 mL)
  7. stirringThe resulting light yellow solution was stirred at room temperature for 2.5 h
  8. customwas quenched with water
  9. extractionextracted with EtOAc
  10. dry with materialThe organic layer was dried over Na2SO4
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated
  13. customPurification of the residue by reversed phase prep
  14. washHPLC (Sunfire Prep C18 OBD 10 μm column, gradient elution of 55% MeCN in water to 85% MeCN in water over a 35 min period, where both solvents

Sources & evidence

ORD record
ord-60c33f9527cb46a5a2c0bd80ff101fea
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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