Water → Vemurafenib

HRID 1098463Notes

Reaction equation

HRID 1098463 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:16]([CH:17]([OH:33])[C:18]4[C:19]([F:32])=[C:20]([NH:25][S:26]([CH2:29][CH2:30][CH3:31])(=[O:28])=[O:27])[CH:21]=[CH:22][C:23]=4[F:24])=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)=[CH:4][CH:3]=1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.O>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:16]([C:17]([C:18]4[C:19]([F:32])=[C:20]([NH:25][S:26]([CH2:29][CH2:30][CH3:31])(=[O:27])=[O:28])[CH:21]=[CH:22][C:23]=4[F:24])=[O:33])=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 58087879HCID 58087879, compound

Product 1

HCID 42611257VemurafenibYield 50%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 632 (ca. 386 mM) in 1,4-dioxane was added 2,3-dichloro-5,6-dicyanobenzoquinone (83.8 g, 502 mM) followed by water (final 4.8%). The resulting mixture was stirred 2 hours at room temperature and then quenched with one volume of saturated sodium bicarbonate. The mixture was evaporated in vacuo to remove 1,4-dioxane and extracted 3× with ethyl acetate. The combined organic layers were dried over sodium sulfate and evaporated in vacuo to give a crude solid that was purified on a silica-gel column with 94:5:1 dichloromethane/methanol/ammonium hydroxide as eluent to give P-0956 (approximately 50% yield for 3 steps) as a white solid.

Workup

  1. customquenched with one volume of saturated sodium bicarbonate
  2. customThe mixture was evaporated in vacuo
  3. customto remove 1,4-dioxane
  4. extractionextracted 3× with ethyl acetate
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. customevaporated in vacuo
  7. customto give a crude solid that
  8. customwas purified on a silica-gel column with 94:5:1 dichloromethane/methanol/ammonium hydroxide as eluent
  9. customto give P-0956 (approximately 50% yield for 3 steps) as a white solid

Sources & evidence

ORD record
ord-8d26021542d44882b6439e93432e0af3
Source dataset
uspto-grants-2012_03
Patent number
US08143271B2

Reaction notes

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