1-Nitro-2-phenylethane → 2(S)-(2-Cyclohexylethyl)-5-(R)-(1-(R)-hydroxy-2-(S)-nitro-3-phenylpropyl)-morpholine-4-carboxylic acid tert-butyl ester

HRID 20370

Reaction equation

HRID 20370 reaction equation
[C:1]1([CH2:7][CH2:8][N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:12]([O:16][C:17]([N:19]1[C@@H:24]([CH:25]=[O:26])[CH2:23][O:22][C@@H:21]([CH2:27][CH2:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[C:12]([O:16][C:17]([N:19]1[C@@H:24]([C@@H:25]([OH:26])[C@@H:8]([N+:9]([O-:11])=[O:10])[CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:23][O:22][C@@H:21]([CH2:27][CH2:28][CH:29]2[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]2)[CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

6

Reactant 3

HCID 802081-Nitro-2-phenylethaneHCID 2724141Tetrabutylammonium FluorideHCID 866153612-(S)-(2-Cyclohexylethyl)-5-(R)-formylmorpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 685582042(S)-(2-Cyclohexylethyl)-5-(R)-(1-(R)-hydroxy-2-(S)-nitro-3-phenylpropyl)-morpholine-4-carboxylic acid tert-butyl esterYield 63.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Add 1-phenyl-2-nitroethane (91 mg, 0.61 mmol) to a solution of 2-(S)-(2-cyclohexylethyl)-5-(R)-formylmorpholine-4-carboxylic acid tert-butyl ester (164 mg, 0.50 mmol) in dry tetrahydrofuran (6 mL). Cool to 0° C. and add tetrabutylammonium fluoride (0.25 mL of a 1 M solution in tetrahydrofuran, 0.25 mmol) and refrigerate the solution overnight. Dilute with ethyl acetate, wash with cold saturated aqueous sodium chloride (50 mL), dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 2.5:97.5 ethyl acetate:dichloromethane) to give the desired compound as a white foam (152 mg, 63%).

Workup

  1. customthe solution overnight
  2. washwash with cold saturated aqueous sodium chloride (50 mL)
  3. dry with materialdry (sodium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate
  6. custompurify
  7. wash(silica gel chromatography, eluting with 2.5:97.5 ethyl acetate:dichloromethane)

Sources & evidence

ORD record
ord-d78273dba6dc49e19ac8e515be59185f
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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