Sodium Chloride → (R)-5-[(1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-2-nitropropyl]-2,2-diphenylmorpholine-4-carboxylic acid tert-butyl ester

HRID 20397Notes

Reaction equation

HRID 20397 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:13]([CH:14]=[O:15])[CH2:12][O:11][C:10]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:28][C:29]1[CH:34]=[C:33]([CH2:35][CH2:36][N+:37]([O-:39])=[O:38])[CH:32]=[C:31]([F:40])[CH:30]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:15])[C@@H:36]([N+:37]([O-:39])=[O:38])[CH2:35][C:33]2[CH:34]=[C:29]([F:28])[CH:30]=[C:31]([F:40])[CH:32]=2)[CH2:12][O:11][C:10]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 552507531,3-Difluoro-5-(2-nitroethyl)benzeneHCID 86615365(R)-5-Formyl-2,2-diphenylmorpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68563474(R)-5-[(1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-2-nitropropyl]-2,2-diphenylmorpholine-4-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To (R)-5-formyl-2,2-diphenylmorpholine-4-carboxylic acid tert-butyl ester (1.03 g, 2.80 mmol) and 1,3-difluoro-5-(2-nitroethyl)-benzene (0.577 g, 3.08 mmol) in tetrahydrofuran (5 mL) at −0° C. under nitrogen add tetrabutylammonium fluoride (3 mL, 3.0 mmol, 1.0 M in tetrahydrofuran). Stir 20 minutes and add half saturated aqueous sodium chloride (20 mL) and ethyl acetate (100 mL). Separate the layers and wash the organic layer with water and saturated aqueous sodium chloride. Dry (magnesium sulfate), filter and concentrate. Purify on silica gel, eluting with 0:100 to 50:50 ethyl acetate:hexanes, then re-crystallize from hexanes/dichloromethane to give the desired compound.

Workup

  1. customSeparate the layers
  2. washwash the organic layer with water and saturated aqueous sodium chloride
  3. dry with materialDry (magnesium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify on silica gel
  7. washeluting with 0:100 to 50:50 ethyl acetate
  8. customhexanes, then re-crystallize from hexanes/dichloromethane

Sources & evidence

ORD record
ord-1469cfe8cdfc4662ac59cec026fa47d2
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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