Potassium Carbonate → 1-{3-Chloro-6-[3-(1,1-dioxo-thiomorpholin-4-yl)-propoxy]-5-[3-(4-fluoro-phenyl)-butoxy]-4-methoxy-2-methyl-phenyl}-ethanone

HRID 219467Notes

Reaction equation

HRID 219467 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]1)(OC(C)(C)C)=O.Br[CH2:17][CH2:18][CH2:19][O:20][C:21]1[C:26]([O:27][CH2:28][CH2:29][CH:30]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[CH3:31])=[C:25]([O:39][CH3:40])[C:24]([Cl:41])=[C:23]([CH3:42])[C:22]=1[C:43](=[O:45])[CH3:44].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[Cl:41][C:24]1[C:23]([CH3:42])=[C:22]([C:43](=[O:45])[CH3:44])[C:21]([O:20][CH2:19][CH2:18][CH2:1][N:8]2[CH2:9][CH2:10][S:11](=[O:14])(=[O:15])[CH2:12][CH2:13]2)=[C:26]([O:27][CH2:28][CH2:29][CH:30]([C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)[CH3:31])[C:25]=1[O:39][CH3:40].[Cl:41][C:24]1[C:23]([CH3:42])=[C:22]([C:43](=[O:45])[CH3:44])[C:21]([O:20][CH2:19][CH2:18][CH2:17][N:8]2[CH2:13][CH2:12][S:11](=[O:14])[CH2:10][CH2:9]2)=[C:26]([O:27][CH2:28][CH2:29][CH:30]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[CH3:31])[C:25]=1[O:39][CH3:40]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 21949260Tert-butyl 1,1-dioxo-1lambda6-thiomorpholine-4-carboxylateHCID 595835011-{2-(3-Bromo-propoxy)-5-chloro-3-[3-(4-fluoro-phenyl)-butoxy]-4-methoxy-6-methyl-phenyl}-ethanone

Product 2

HCID 252546821-{3-Chloro-5-[3-(4-fluoro-phenyl)-butoxy]-4-methoxy-2-methyl-6-[3-(1-oxo-thiomorpholin-4-yl)-propoxy]-phenyl}-ethanoneYield 13%HCID 252546831-{3-Chloro-6-[3-(1,1-dioxo-thiomorpholin-4-yl)-propoxy]-5-[3-(4-fluoro-phenyl)-butoxy]-4-methoxy-2-methyl-phenyl}-ethanoneYield 14%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of N—BOC-1,1-dioxothiomorpholine (85 mg, 0.365 mmol) in a mixture of DCM (1 mL) and TFA (1 mL) was stirred at room temperature for 0.1 h before concentrating under vacuum and drying the TFA salt of 1,1-dioxothiomorpholine on the high vacuum pump for 3 h. The salt was dissolved in dry DMF (1 mL) and reacted with Example 22a (92 mg, 0.18 mmol) and K2CO3 (2.16 eq.) under General Procedure L. The crude mixture was purified by flash chromatography (silica gel, hexane/Et2O 1:4→MeOH/DCM 1:19) to afford 23 (14 mg, 14%) and 24 (13 mg, 13%) as clear colourless oils.

Workup

  1. concentrationbefore concentrating under vacuum
  2. dry with materialdrying the TFA salt of 1,1-dioxothiomorpholine on the high vacuum pump for 3 h
  3. dissolutionThe salt was dissolved in dry DMF (1 mL)
  4. customThe crude mixture was purified by flash chromatography (silica gel, hexane/Et2O 1:4→MeOH/DCM 1:19)

Sources & evidence

ORD record
ord-d89ead20c28b4d1fb0e0ab5a5bfe7154
Source dataset
uspto-grants-2012_06
Patent number
US08202513B2

Reaction notes

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