Hydrogen Peroxide → ditert-butyl(1S,2S,4S,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylate

HRID 2172985Notes

Reaction equation

HRID 2172985 reaction equation
C([BH-](C(CC)C)C(CC)C)(CC)C.[Li+].[C:15]([O:19][C:20]([NH:22][C@@:23]1([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:28][C:27](=[O:29])[C@@H:26]2[C@H:24]1[C@H:25]2[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:21])([CH3:18])([CH3:17])[CH3:16].C(=O)(O)[O-].[Na+].OO>O1CCCC1>[C:15]([O:19][C:20]([NH:22][C@@:23]1([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:28][C@H:27]([OH:29])[C@@H:26]2[C@H:24]1[C@H:25]2[C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 516892Sodium BicarbonateHCID 3611392Lithium tri-s-butylborohydrideHCID 59712878Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-[[(1,1-dimethylethoxy)carbonyl]amino]-4-oxo-, 2,6-bis(1,1-dimethylethyl) ester, (1S,2S,5R,6R)-

Product 1

HCID 59712892ditert-butyl(1S,2S,4S,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylateYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Add 1M lithium tri(sec-butyl)borohydride in tetrahydrofuran (42.27 mL, 42.27 mmol) dropwise to di-tert-butyl (1S,2S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylate (7.10 g, 17.25 mmol, see WO03/104217/A2 for synthesis details) in tetrahydrofuran (431.35 mL) at 0° C. and stir. After 90 minutes, carefully add 1M aqueous sodium bicarbonate (60.07 mL, 62.11 mmol) followed by hydrogen peroxide (30% wt, 2.64 mL, 86.27 mmol) at 0° C. The reaction is warmed to room temperature. After 40 minutes, the reaction is extracted with ethyl acetate, washed with 10% aqueous citric acid followed by brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a residue. The residue is purified by flash chromatography eluting with 5-50% ethyl acetate in hexanes to give the title compound (6.70 g, 16.20 mmol, 94%).

Workup

  1. customat 0° C
  2. waitAfter 40 minutes
  3. extractionthe reaction is extracted with ethyl acetate
  4. washwashed with 10% aqueous citric acid
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give a residue
  9. customThe residue is purified by flash chromatography
  10. washeluting with 5-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6d23371289af42b0a816ada74ddc5819
Source dataset
uspto-grants-2015_06
Patent number
US09056844B2

Reaction notes

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