Triethylamine → (9S)-9-[4-(4-chlorophenoxy)phenyl]-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1748012Notes

Reaction equation

HRID 1748012 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=1.[O:18]=[S:19]1(=[O:36])[CH2:24][CH2:23][N:22]2[CH2:25][CH2:26][CH2:27][C@@H:28]([C:29]3[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=3)[C:21]2=[N:20]1>CN(C=O)C.C(O[Cu]OC(=O)C)(=O)C>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([O:35][C:32]2[CH:31]=[CH:30][C:29]([C@H:28]3[C:21]4=[N:20][S:19](=[O:36])(=[O:18])[CH2:24][CH2:23][N:22]4[CH2:25][CH2:26][CH2:27]3)=[CH:34][CH:33]=2)=[CH:11][CH:10]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 742994-Chlorophenylboronic acid2×HCID 667484964-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenol

Product 1

HCID 66748008(9S)-9-[4-(4-chlorophenoxy)phenyl]-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxideYield 15.9%

Reagents, catalysts & solvents 2

HCID 178476681HCID 178476681, compoundCatalyst2×HCID 6228DimethylformamideSolvent

Procedure

Diacetoxycopper (1037 mg) was added to a mixture of triethylamine (1.983 mL), 4-chlorophenylboronic acid (1339 mg), 4-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenol (800 mg) and in DMF (dry) (30 mL). The mixture was stirred at room temperature under a dry atmosphere with anhydrous calcium chloride tube for 15 hr. Then 4-chlorophenylboronic acid (1339 mg) and diacetoxycopper (1037 mg) were added and the mixture was stirred at room temperature under a dry atmosphere with anhydrous calcium chloride tube for 2 days. The insoluble material was removed by filtration, and the filtrate was diluted with water, and extracted with EtOAc. The organic layer was washed with 0.1N NaOH aq., dried over anhydrous magnesium sulfate. Silica-gel was added and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc) then crystallized from THF/IPE to give the title compound (177 mg) as an off-white solid.

Workup

  1. stirringthe mixture was stirred at room temperature under a dry atmosphere with anhydrous calcium chloride tube for 2 days
  2. customThe insoluble material was removed by filtration
  3. additionthe filtrate was diluted with water
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with 0.1N NaOH aq.
  6. dry with materialdried over anhydrous magnesium sulfate
  7. additionSilica-gel was added
  8. customthe volatiles were removed in vacuo
  9. customwas purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc)
  10. customthen crystallized from THF/IPE

Sources & evidence

ORD record
ord-80851a8a1f7d491b87d65c7f7edcbf98
Source dataset
uspto-grants-2015_10
Patent number
US09150591B2

Reaction notes

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