Sodium Bicarbonate → (1R,2R,3S,5R,6R)-2-amino-6-fluoro-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester

HRID 130507Notes

Reaction equation

HRID 130507 reaction equation
CP(C)C.O1CCCC1.[CH2:10]([O:12][C:13]([C@:15]1([N:28]=[N+]=[N-])[C@@H:20]([OH:21])[CH2:19][C@@H:18]2[C@H:16]1[C@@:17]2([F:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[O:14])[CH3:11].C(=O)([O-])O.[Na+]>O1CCCC1.O.C(OCC)C>[CH2:10]([O:12][C:13]([C@:15]1([NH2:28])[C@@H:20]([OH:21])[CH2:19][C@@H:18]2[C@H:16]1[C@@:17]2([F:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[O:14])[CH3:11]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 11185694(1R,2R,3S,5R,6R)-2-azido-6-fluoro-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl esterHCID 86589763trimethylphosphine THF

Product 1

HCID 11288856(1R,2R,3S,5R,6R)-2-amino-6-fluoro-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl esterYield 72.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

0.89 mL of a solution of 1M trimethylphosphine/tetrahydrofuran was added to 245 mg of (1R,2R,3S,5R,6R)-2-azido-6-fluoro-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester dissolved in 7.0 mL of tetrahydrofuran and 0.7 mL of water, and the mixture was stirred for 12 hours at room temperature. After the mixture was diluted with 14 mL of diethyl ether, a saturated aqueous solution of sodium hydrogen carbonate was added thereto, and the mixture was stirred for 1 hour at room temperature. After separation, the aqueous layer was extracted twice with chloroform. The organic layers were combined, washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. The desiccant was filtered off, and the filtrate was concentrated under reduced pressure The residue was purified by column chromatography (silica gel: Wako gel C200 (made by Wako Pure Chemical Industries Ltd.), eluent: chloroform-ethanol=50:1), thereby yielding 163 mg of (1R,2R,3S,5R,6R)-2-amino-6-fluoro-3-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid diethyl ester.

Workup

  1. customAfter separation
  2. extractionthe aqueous layer was extracted twice with chloroform
  3. washwashed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe desiccant was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure The residue
  7. customwas purified by column chromatography (silica gel: Wako gel C200 (made by Wako Pure Chemical Industries Ltd.), eluent: chloroform-ethanol=50:1)

Sources & evidence

ORD record
ord-7c28b5994f68413682f3b760143cf0e1
Source dataset
uspto-grants-2008_06
Patent number
US07381746B2

Reaction notes

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