4-Nitrobenzoic Acid → 4-nitrobenzoic acid (S)-1-[(3R,5R)-5-(4-chlorophenyl)morpholin-3-yl]ethyl ester

HRID 1677065Notes

Reaction equation

HRID 1677065 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C@H:22]2[NH:27][C@@H:26]([C@H:28]([OH:30])[CH3:29])[CH2:25][O:24][CH2:23]2)=[CH:18][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+:50]([C:53]1[CH:61]=[CH:60][C:56]([C:57](O)=[O:58])=[CH:55][CH:54]=1)([O-:52])=[O:51]>C(OCC)(=O)C.O.O1CCCC1>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([C@H:22]2[NH:27][C@@H:26]([C@@H:28]([O:30][C:57](=[O:58])[C:56]3[CH:55]=[CH:54][C:53]([N+:50]([O-:52])=[O:51])=[CH:61][CH:60]=3)[CH3:29])[CH2:25][O:24][CH2:23]2)=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 67371750(R)-1-[(3R,5R)-5-(4-chlorophenyl)morpholin-3-yl]ethanol

Product 1

HCID 673717534-nitrobenzoic acid (S)-1-[(3R,5R)-5-(4-chlorophenyl)morpholin-3-yl]ethyl esterYield 100%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under a nitrogen atmosphere and under ice-cooling, diisopropylazodicarboxylate (1.36 mL) was added dropwise in a tetrahydrofuran solution containing (R)-1-[(3R,5R)-5-(4-chlorophenyl)morpholin-3-yl]ethanol (903 mg), triphenylphosphine (1.81 g), and 4-nitrobenzoic acid (1.16 g). Stirring was continued for 30 minutes at the same temperature and for 2 hours at room temperature. Water and ethyl acetate was added to the reaction solution, and the organic layer was partitioned. The organic layer was washed with brine and was dried over anhydrous magnesium sulfate. The solvent was removed under a vacuum, and the residue was purified by silica gel column chromatography (heptane/ethyl acetate 9/1→8/2→7/3), and the title compound (1.46 g) was obtained. The physical property values are as follows.

Workup

  1. temperatureUnder a nitrogen atmosphere and under ice-cooling
  2. customthe organic layer was partitioned
  3. washThe organic layer was washed with brine
  4. dry with materialwas dried over anhydrous magnesium sulfate
  5. customThe solvent was removed under a vacuum
  6. customthe residue was purified by silica gel column chromatography (heptane/ethyl acetate 9/1→8/2→7/3)

Sources & evidence

ORD record
ord-aeb90c0291514159983613fdf2b4b66c
Source dataset
uspto-grants-2011_08
Patent number
US08008293B2

Reaction notes

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