1-Nitro-2-phenylethane → (2R,4S)-tert-butyl 4-fluoro-2-((1R,2S)-1-hydroxy-2-nitro-3-phenylpropyl)pyrrolidine-1-carboxylate

HRID 732353Notes

Reaction equation

HRID 732353 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]1([CH2:25][CH2:26][N+:27]([O-:29])=[O:28])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[C:30]([O:34][C:35]([N:37]1[CH2:41][C@@H:40]([F:42])[CH2:39][C@@H:38]1[CH:43]=[O:44])=[O:36])([CH3:33])([CH3:32])[CH3:31]>C1COCC1.C(OCC)(=O)C>[C:30]([O:34][C:35]([N:37]1[CH2:41][C@@H:40]([F:42])[CH2:39][C@@H:38]1[C@H:43]([OH:44])[C@@H:26]([N+:27]([O-:29])=[O:28])[CH2:25][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:36])([CH3:33])([CH3:32])[CH3:31].[C:30]([O:34][C:35]([N:37]1[CH2:41][C@@H:40]([F:42])[CH2:39][C@@H:38]1[C@@H:43]([OH:44])[C@@H:26]([N+:27]([O-:29])=[O:28])[CH2:25][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:36])([CH3:33])([CH3:32])[CH3:31]

Participants

7

Reactant 3

HCID 802081-Nitro-2-phenylethaneHCID 2724141Tetrabutylammonium FluorideHCID 86614993HCID 86614993, compound

Product 2

HCID 68814538(2R,4S)-tert-butyl 4-fluoro-2-((1R,2S)-1-hydroxy-2-nitro-3-phenylpropyl)pyrrolidine-1-carboxylateYield 46%HCID 688159854-(S)-fluoro-2-(R)-(1-(S)-hydroxy-2-(S)-nitro-3-phenylpropyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 29%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Add tetrabutylammonium fluoride (2.0 mL of 1.0 M solution in THF) to an ice-cold solution of 1-phenyl-2-nitroethane (0.51 mL, 3.79 mmol) in THF (2 mL). Stir 5 min and add 4-(S)-fluoro-2-(R)-formylpyrrolidine-1-carboxylic acid tert-butyl ester (0.58 g, 1.95 mmol) in THF (6 mL). Stir 90 min, dilute with ethyl acetate, wash with water (3×50 mL), saturated aqueous sodium chloride, dry (magnesium sulfate) and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compounds as foams, 4-(S)-fluoro-2-(R)-(1-(S)-hydroxy-2-(S)-nitro-3-phenylpropyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.21 g, 29%) and 4-(S)-fluoro-2-(R)-(1-(R)-hydroxy-2-(S)-nitro-3-phenylpropyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.33 g, 46%).

Workup

  1. stirringStir 90 min
  2. washwash with water (3×50 mL), saturated aqueous sodium chloride
  3. dry with materialdry (magnesium sulfate)
  4. custompurify
  5. wash(silica gel chromatography, eluting with hexanes and ethyl acetate)

Sources & evidence

ORD record
ord-f3be2e5ba6824efe9085d1dcaffe2d14
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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