Tetrabutylammonium Fluoride → (2R,5R)-5-[(1R,2S)-3-(3-Chloro-5-fluorophenyl)-1-hydroxy-2-nitropropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester

HRID 20361Notes

Reaction equation

HRID 20361 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][N+:10]([O-:12])=[O:11])[CH:5]=[C:4]([F:13])[CH:3]=1.[C:14]([O:18][C:19]([N:21]1[C@@H:26]([CH:27]=[O:28])[CH2:25][O:24][C@@H:23]([O:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[C:14]([O:18][C:19]([N:21]1[C@@H:26]([C@@H:27]([OH:28])[C@@H:9]([N+:10]([O-:12])=[O:11])[CH2:8][C:6]2[CH:5]=[C:4]([F:13])[CH:3]=[C:2]([Cl:1])[CH:7]=2)[CH2:25][O:24][C@@H:23]([O:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 685589231-Chloro-3-fluoro-5-(2-nitroethyl)benzeneHCID 86615359(2R,5R)-2-(2,2-Dimethylpropoxy)-5-formylmorpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68562233(2R,5R)-5-[(1R,2S)-3-(3-Chloro-5-fluorophenyl)-1-hydroxy-2-nitropropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl esterYield 59%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Add 1-chloro-3-fluoro-5-(2-nitroethyl)-benzene (0.343 g, 1.68 mmol) in dry tetrahydrofuran (2 mL) to a solution of (2R,5R)-2-(2,2-dimethylpropoxy)-5-formylmorpholine-4-carboxylic acid tert-butyl ester (0.462 g, 1.53 mmol) in tetrahydrofuran (7 mL). Add tetrabutylammonium fluoride (0.77 mL, 0.765 mmol, 1.0 M in tetrahydrofuran) and stir at room temperature for 1 hour. Dilute with ethyl acetate and wash with saturated aqueous sodium chloride, dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 2:98 ethyl acetate:dichloromethane) to give the desired compound as a white foam (0.455 g, 59%).

Workup

  1. washwash with saturated aqueous sodium chloride
  2. dry with materialdry (sodium sulfate)
  3. concentrationconcentrate
  4. custompurify
  5. wash(silica gel chromatography, eluting with 2:98 ethyl acetate:dichloromethane)

Sources & evidence

ORD record
ord-f6f354ef83aa403eafec4285b37b86e6
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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