HCID 86667410, compound → HCID 68171039, compound

HRID 1429079Notes

Reaction equation

HRID 1429079 reaction equation
[C:1]([O:5][C:6]([N:8]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@:9]1([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][C@H:10]1[CH2:12][CH:13]=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:27]([Mg]Br)[CH2:28][CH:29]=[CH2:30]>O1CCCC1>[C:1]([O:5][C:6]([N:8]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[C@:9]1([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][C@H:10]1[CH2:12][CH:13]([OH:14])[CH2:30][CH2:29][CH:28]=[CH2:27])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 86667410HCID 86667410, compoundHCID 178418797HCID 178418797, compound

Product 1

HCID 68171039HCID 68171039, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1R,2S)-ethyl 1-(bis(tert-butoxycarbonyl)amino)-2-(2-hydroxyethyl)cyclopropanecarboxylate (8.65 g, 23.2 mmol) in dichloromethane (116 ml) at 25° C. was added Dess-Martin Periodinane (13.8 g, 32.4 mmol). The mixture was stirred for 3 h and quenched with 1 N sodium thiosulfate (70 mL) and aqueous saturated sodium bicarbonate solution (30 mL), and stirred for 1 h. The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure. This material was purified by flash chromatography on silica gel (eluted with 25% ethyl acetate/hexane) to yield (1R,2S)-ethyl 1-(bis(tert-butoxycarbonyl)amino)-2-(2-oxoethyl)cyclopropanecarboxylate (7.05 g, 82% yield) as an oil. MS (ESI): m/z=394.1 [M+Na]. To (1R,2S)-ethyl 1-(bis(tert-butoxycarbonyl)amino)-2-(2-oxoethyl)cyclopropanecarboxylate (7.05 g, 19.0 mmol) in tetrahydrofuran (60 mL) at −78° C. was added but-3-enylmagnesium bromide (45.6 mL, 22.78 mmol) and the reaction mixture was stirred for 30 min. The mixture was then quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The residual oil was purified via flash chromatography on silica gel (25% hexane/ethyl acetate) to provide the title compound (2.75 g, 34%) as an oil, along with recovered starting material (2.89 g, 41%). MS (ESI): m/z=450.1 [M+Na].

Workup

  1. customThe mixture was then quenched with saturated aqueous ammonium chloride
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residual oil was purified via flash chromatography on silica gel (25% hexane/ethyl acetate)

Sources & evidence

ORD record
ord-add6d16781904552b79e007f1fcd8362
Source dataset
uspto-grants-2015_01
Patent number
US08937041B2

Reaction notes

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