Sodium;3-oxidodioxaborirane;tetrahydrate → HCID 68171037, compound

HRID 1429077Notes

Reaction equation

HRID 1429077 reaction equation
[C:1]([O:5][C:6]([N:8]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C@:9]1([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:11][C@H:10]1[CH:12]=[CH2:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].B1([O-])O[O:27]1.O.O.O.O.[Na+]>O1CCCC1.C(OCC)(=O)C.O>[C:1]([O:5][C:6]([N:8]([C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20])[C@:9]1([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:11][C@H:10]1[CH2:12][CH2:13][OH:27])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 23693097Sodium;3-oxidodioxaborirane;tetrahydrateHCID 57740081HCID 57740081, compound

Product 1

HCID 68171037HCID 68171037, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

To (1R,2S)-ethyl 1-(tert-butoxycarbonylamino)-2-vinylcyclopropanecarboxylate (10 g, 39.2 mmol) and Boc anhydride (22.73 mL, 98 mmol) dissolved in tetrahydrofuran (25 mL) at room temperature was added portionwise DMAP (3.83 g, 31.3 mmol) and the mixture was stirred for 3 h. The mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with 0.1 N HCl followed by saturated aqueous sodium chloride solution, separated, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The residual oil was purified by flash chromatography on silica gel eluting with a 5-15% ethyl acetate/hexane gradient to provide (1R,2S)-ethyl 1-(bis(tert-butoxycarbonyl)amino)-2-vinylcyclopropanecarboxylate (13.2 g, 37.1 mmol, 95% yield) as a clear oil. MS (ESI): m/z=378.0 [M+Na]. To a solution of (1R,2S)-ethyl 1-(bis(tert-butoxycarbonyl)amino)-2-vinylcyclopropane carboxylate (13.2 g, 37.1 mmol) in tetrahydrofuran (50 mL) at -15° C. was added dropwise 1 N borane tetrahydrofuran complex (74.3 mL, 74.3 mmol) and the mixture was stirred for 2 h at −15° C. To the resulting mixture stirring at 0° C. was added dropwise water (100 mL) followed by sodium perborate tetrahydrate (11.43 g, 74.3 mmol), and the mixture was stirred for 16 hr at rt. The reaction mixture was diluted with ethyl acetate and water, and the resulting organic layer was washed with saturated aqueous sodium chloride solution, separated, dried over anhydrous magnesium sulfate, filtered, and the solvent evaporated under reduced pressure. The residue was purified via flash chromatography on silica gel (10-20% acetone/hex). The resulting impure material was repurified by flash chromatography on silica gel (eluting with a 25%-50% ethyl acetate/hexane gradient) to give (1R,2S)-ethyl 1-(bis(tert-butoxycarbonyl)amino)-2-(2-hydroxyethyl)cyclopropanecarboxylate (9.15 g, 24.50 mmol, 66.0% yield) as an oil. MS (ESI): m/z=396.0 [M+Na].

Workup

  1. stirringTo the resulting mixture stirring at 0° C.
  2. stirringthe mixture was stirred for 16 hr at rt
  3. washthe resulting organic layer was washed with saturated aqueous sodium chloride solution
  4. customseparated
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customThe residue was purified via flash chromatography on silica gel (10-20% acetone/hex)
  9. customThe resulting impure material was repurified by flash chromatography on silica gel (
  10. washeluting with a 25%-50% ethyl acetate/hexane gradient)

Sources & evidence

ORD record
ord-323379da3a214cf2b9b9665532be513b
Source dataset
uspto-grants-2015_01
Patent number
US08937041B2

Reaction notes

Loading…