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

HRID 2173005Notes

Reaction equation

HRID 2173005 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+].[Na+].OO>O1CCCC1.O>[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

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 10340Sodium CarbonateHCID 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 86.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

Add 1M lithium tri(sec-butyl)borohydride in tetrahydrofuran (2.67 L, 2.67 mol) dropwise to a solution of di-tert-butyl(1S,2S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylate (1000 g, 2.43 mol) in dry tetrahydrofuran (10 L) at 0° C. under nitrogen. After 2 hours at 0° C., 2M Na2CO3 in water (850 g, 8.02 mol) is added at 0° C. over 2 hours followed by 35% aqueous hydrogen peroxide (740 mL, 8.99 mol) in water (3.3 L). After 40 minutes, the mixture is warmed to ambient temperature whereupon the organic phase is separated. The organic phase is diluted with methyl tert-butyl ether (3.5 L) and the layers are separated again. The aqueous phase is extracted with methyl tert-butyl ether (3.5 L). All the combined organic phases are washed successively with 1M aqueous Na2SO3 (2.67 L), water (2.67 L), and brine (2.67 L), dried over sodium sulfate, filtered and concentrated to a volume of 3 L. The precipitated solid is filtered and washed with heptane (1.3 L) to obtain the title compound (864.76 g). The mother liquors are concentrated to dryness and the residue is triturated with heptane (500 mL) and filtered to obtain additional title compound (130.64 g, total 995.4 g, yield 99%). MS (m/z): 436 (M+23).

Workup

  1. waitAfter 40 minutes
  2. customis separated
  3. additionThe organic phase is diluted with methyl tert-butyl ether (3.5 L)
  4. customthe layers are separated again
  5. extractionThe aqueous phase is extracted with methyl tert-butyl ether (3.5 L)
  6. washAll the combined organic phases are washed successively with 1M aqueous Na2SO3 (2.67 L), water (2.67 L), and brine (2.67 L)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to a volume of 3 L
  10. filtrationThe precipitated solid is filtered
  11. washwashed with heptane (1.3 L)

Sources & evidence

ORD record
ord-2b66347230aa4ba981b33a6e74dc98be
Source dataset
uspto-grants-2015_06
Patent number
US09056844B2

Reaction notes

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