tert-Butanol → 6-(4-Bromo-2-methyl-phenylamino)-3-(4,5-dihydroxy-pentyl)-7-fluoro-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 31988Notes

Reaction equation

HRID 31988 reaction equation
[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:22]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([Br:30])=[CH:26][C:25]=3[CH3:31])=[C:21]([F:32])[C:12]3[N:13]=[CH:14][N:15]([CH2:16][CH2:17]CC=C)[C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1.C[N+]1([O-])CC[O:37]CC1.[CH3:41][C:42]([OH:45])(C)[CH3:43]>C1COCC1.O.O=[Os](=O)(=O)=O>[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:22]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([Br:30])=[CH:26][C:25]=3[CH3:31])=[C:21]([F:32])[C:12]3[N:13]=[CH:14][N:15]([CH2:16][CH2:17][CH2:41][CH:42]([OH:45])[CH2:43][OH:37])[C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 6386tert-ButanolHCID 82029Methyl morpholine oxideHCID 588906146-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

Product 1

HCID 865990166-(4-Bromo-2-methyl-phenylamino)-3-(4,5-dihydroxy-pentyl)-7-fluoro-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amideYield 74%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-pent-4-enyl-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide 11f (0.307 g, 0.612 mmol) is dissolved in 4:1 THF/water (8 mL) and 1.134 mL (0.061 mmol) of an 0.054 M OsO4 solution in t-BuOH iias added followed by NMO (0.093 g, 0.796 mmol). After 5 hours, the reaction mixture is quenched by the addition of 10% NaHS2O3 solution. After 10 minutes, the reaction mixture is filtered through Celite rinsing with ethyl acetate and methylene chloride. The filtrate is diluted with ethyl acetate and washed with 0.01 N HCl, and brine. The organic layer is dried (Na2SO4) and concentrated under reduced pressure. The crude product is purified by FCC eluted with 9:1 ethyl acetate/MeOH to give 0.244 g (74%) pure desired product.

Workup

  1. additionadded
  2. customthe reaction mixture is quenched by the addition of 10% NaHS2O3 solution
  3. waitAfter 10 minutes
  4. filtrationthe reaction mixture is filtered through Celite
  5. washrinsing with ethyl acetate and methylene chloride
  6. additionThe filtrate is diluted with ethyl acetate
  7. washwashed with 0.01 N HCl, and brine
  8. dry with materialThe organic layer is dried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product is purified by FCC
  11. washeluted with 9:1 ethyl acetate/MeOH

Sources & evidence

ORD record
ord-86dfd9b88626460fa64aba819795cb72
Source dataset
uspto-grants-2008_09
Patent number
US07425637B2

Reaction notes

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