Triethylamine → HCID 58026125, compound

HRID 2387335Notes

Reaction equation

HRID 2387335 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:20])([CH3:19])[CH2:9][C@@:10]([C:15]([F:18])([F:17])[F:16])([OH:14])[CH2:11][C:12]#[CH:13])=[C:4]([S:21]([CH3:24])(=[O:23])=[O:22])[CH:3]=1.C(N(CC)CC)C.[C:32]([O:36][C:37](=[O:50])[NH:38][C:39]1[CH:40]=[N:41][C:42]([S:46]([CH3:49])(=[O:48])=[O:47])=[CH:43][C:44]=1I)([CH3:35])([CH3:34])[CH3:33].[Cl-].[NH4+]>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C>[C:32]([O:36][C:37](=[O:50])[NH:38][C:39]1[CH:40]=[N:41][C:42]([S:46]([CH3:49])(=[O:48])=[O:47])=[CH:43][C:44]=1[C:13]#[C:12][CH2:11][C@@:10]([OH:14])([C:15]([F:16])([F:18])[F:17])[CH2:9][C:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=1[S:21]([CH3:24])(=[O:22])=[O:23])([CH3:20])[CH3:19])([CH3:35])([CH3:34])[CH3:33]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 44544528HCID 44544528, compoundHCID 58026149HCID 58026149, compound

Product 1

HCID 58026125HCID 58026125, compoundYield 68%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-6-(4-chloro-2-methanesulfonylphenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol (15.6 g, 40.8 mmol), triethylamine (23.0 mL, 165 mmol), and (4-iodo-6-methanesulfonylpyridin-3-yl)carbamic acid tert-butyl ester (18.0 g, 45.2 mmol) in 150 mL of DMF was added CuI (1.6 g, 8.4 mmol) and Pd(PPh3)2Cl2 (3.0 g, 4.3 mmol) as one mixed solid batch. The mixture was stirred at room temperature for 18 hours resulting in the color changing to deep red. Saturated aqueous ammonium chloride solution and ethyl acetate were added. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water, brine, dried over sodium sulfate, filtered through CELITE® filter aid, and evaporated. The crude material was separated by flash column chromatography using a 0-75% EtOAc/hexanes gradient. Evaporation of the solvent yielded an off-white foam as the pure {4-[(S)-6-(4-chloro-2-methanesulfonylphenyl)-4-hydroxy-6-methyl-4-trifluoromethylhept-1-ynyl]-6-methanesulfonylpyridin-3-yl}carbamic acid tert-butyl ester (18.1 g, 68%).

Workup

  1. customresulting in the color
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with water, brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered through CELITE®
  6. filtrationfilter aid
  7. customevaporated
  8. customThe crude material was separated by flash column chromatography
  9. customEvaporation of the solvent

Sources & evidence

ORD record
ord-f487ab2249654e35a1a885a04429d062
Source dataset
uspto-grants-2012_09
Patent number
US08268859B2

Reaction notes

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