Hydrogen Peroxide → HCID 86707931, compound

HRID 1396032Notes

Reaction equation

HRID 1396032 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]([C:12]1[N:13]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[C:31]([S:33]([CH3:36])(=[O:35])=[O:34])[C:30]([CH2:37][OH:38])=[C:29]([F:39])[CH:28]=3)=[CH:23][C:22]=2[F:40])[CH:14]=[C:15]([C:17]([OH:20])([CH3:19])[CH3:18])[N:16]=1)([CH3:11])[CH3:10].C(N(C(C)C)[P:45]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])(C)C.N1C=NN=N1.[OH:64]O>>[P:45]([O:38][CH2:37][C:30]1[C:31]([S:33]([CH3:36])(=[O:34])=[O:35])=[CH:32][C:27]([C:24]2[CH:25]=[CH:26][C:21]([N:13]3[CH:14]=[C:15]([C:17]([OH:20])([CH3:18])[CH3:19])[N:16]=[C:12]3[C:9]([C:3]3[C:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])([CH3:10])[CH3:11])=[C:22]([F:40])[CH:23]=2)=[CH:28][C:29]=1[F:39])([O:46][C:47]([CH3:48])([CH3:49])[CH3:50])([O:51][C:52]([CH3:53])([CH3:54])[CH3:55])=[O:64]

Participants

5

Reactant 4

HCID 784Hydrogen PeroxideHCID 853005Di-tert-butyl N,N-DiisopropylphosphoramiditeHCID 49787490Bms-852927HCID 178418441HCID 178418441, compound

Product 1

HCID 86707931HCID 86707931, compoundYield 37%

Procedure

To a solution of 2-(2-(1-(2,6-dichlorophenyl)-1-methylethyl)-1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)-4-biphenylyl)-1H-imidazol-4-yl)-2-propanol (prepared in the manner described in PCT Publication No. WO 2010/138598, 1.98 g, 3.25 mmol) and di-tert-butyl diisopropylphosphoramidite (1.35 g, 4.87 mmol) in CH2CH2 (10 mL) was added tetrazole (0.569 g, 8.13 mmol). The resulting suspension was stirred at rt for about 16 hours. After this time, hydrogen peroxide (30%, 8.13 mmol) was added drop-wise and the resulting mixture was stirred for 2 hours. At the conclusion of this period, the reaction mixture was diluted with CH2CH2 (10 mL), washed with brine, dried and then concentrated to yield the crude product. The crude product was purified by column chromatography (hexane and acetone gradient; 9:1 to 1:1) to afford di-tert-butyl (4′-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-4-(2-hydroxypropan-2-yl)-1H-imidazol-1-yl)-3,3′-difluoro-5-(methylsulfonyl)biphenyl-4-yl)methyl phosphate (0.960 g, 1.20 mmol, 37% yield) as a white solid.

Workup

  1. stirringthe resulting mixture was stirred for 2 hours
  2. additionAt the conclusion of this period, the reaction mixture was diluted with CH2CH2 (10 mL)
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated
  6. customto yield the crude product
  7. customThe crude product was purified by column chromatography (hexane and acetone gradient; 9:1 to 1:1)

Sources & evidence

ORD record
ord-ab3e3bf130364268bfa9806acf9a1b96
Source dataset
uspto-grants-2014_12
Patent number
US08901106B2

Reaction notes

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