(Diethylamino)sulfur trifluoride → HCID 178499255, compound

HRID 1190044Notes

Reaction equation

HRID 1190044 reaction equation
C(N(S(F)(F)[F:7])CC)C.[CH3:10][O:11][C:12]([C:14]1[S:15][C:16]([Br:36])=[CH:17][C:18]=1[N:19]([C@H:29]1[CH2:34][CH2:33][C@H:32](O)[CH2:31][CH2:30]1)[C:20]([C@H:22]1[CH2:27][CH2:26][C@H:25]([CH3:28])[CH2:24][CH2:23]1)=[O:21])=[O:13].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:10][O:11][C:12]([C:14]1[S:15][C:16]([Br:36])=[CH:17][C:18]=1[N:19]([C@H:29]1[CH2:34][CH2:33][C@@H:32]([F:7])[CH2:31][CH2:30]1)[C:20]([C@H:22]1[CH2:27][CH2:26][C@H:25]([CH3:28])[CH2:24][CH2:23]1)=[O:21])=[O:13].[CH3:10][O:11][C:12]([C:14]1[S:15][C:16]([Br:36])=[CH:17][C:18]=1[N:19]([C@H:29]1[CH2:34][CH2:33][C@H:32]([F:7])[CH2:31][CH2:30]1)[C:20]([C@H:22]1[CH2:27][CH2:26][C@H:25]([CH3:28])[CH2:24][CH2:23]1)=[O:21])=[O:13]

Participants

6

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 178499257HCID 178499257, compound

Product 2

HCID 178499255HCID 178499255, compoundYield 18%HCID 178499256HCID 178499256, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (diethylamino)sulfur trifluoride (0.24 mL, 1.82 mmol) in DCM (2.7 mL) pyridine (0.27 mL, 3.34 mmol) was added followed by dropwise addition of 5-bromo-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (150 mg, 0.32 mmol) in DCM (2.0 mL) during 10 min. The mixture was stirred for 16 h at room temperature. It was cooled in ice-bath and saturated NaHCO3 was added slowly to neutralize the excess reagent. The mixture was stirred at room temperature for 3 h. It was extracted with DCM (100 mL), washed with brine, dried (MgSO4) and evaporated. The crude was chromatographed over silica gel (hexane:EtOAc-95:5 and 90:10 as eluents) yielding pure 5-bromo-3-[(cis-4-fluoro-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (28 mg, 18%) and 5-bromo-3-[(trans-4-fluoro-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (22 mg, 14%).

Workup

  1. temperatureIt was cooled in ice-bath
  2. stirringThe mixture was stirred at room temperature for 3 h
  3. extractionIt was extracted with DCM (100 mL)
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe crude was chromatographed over silica gel (hexane:EtOAc-95:5 and 90:10 as eluents)

Sources & evidence

ORD record
ord-b915c09ee8834b04a2d3332af43f68cf
Source dataset
uspto-grants-2014_03
Patent number
US08674118B2

Reaction notes

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