4-Chlorobenzaldehyde → HCID 58610187, compound

HRID 1592829Notes

Reaction equation

HRID 1592829 reaction equation
[Li].[CH2:2]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][C:10]1=[O:15])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[O:22])=[CH:19][CH:18]=1>CCCCCCC.O1CCCC1>[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([C@H:21]([OH:22])[C@H:11]2[O:12][CH2:13][CH2:14][N:9]([CH2:2][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:10]2=[O:15])=[CH:19][CH:18]=1.[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([C@@H:21]([OH:22])[C@@H:11]2[O:12][CH2:13][CH2:14][N:9]([CH2:2][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:10]2=[O:15])=[CH:19][CH:18]=1

Participants

7

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 3028194LithiumHCID 122940874-Benzylmorpholin-3-one

Product 2

HCID 58610175HCID 58610175, compoundHCID 58610187HCID 58610187, compoundYield 61.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8900HeptaneSolvent

Conditions

Temperature
-70 °C

Procedure

A solution of lithium diisopropylanide (2M in heptane, 18.2 ml) was added dropwise over 20 min to a stirred solution of 4-benzyl-morpholin-3-one (5.0 g, 26 mmol) and 4-chlorobenzaldehyde (4.41 g, 31.4 mmol) in dried tetrahydrofuran (60 ml) cooled to −70° C. under nitrogen atmosphere. After 1 h at −70° C., the reaction mixture was quenched with aqueous ammonium chloride (100 ml) and extracted with ethyl acetate (100 ml). The extracts were washed with 2M aqueous hydrochloric acid (100 ml), brine solution (100 ml) and dried over sodium sulphate. After filtration, the solution was evaporated and the residual oil purified by chromatography on silica eluting with ethyl acetate:hexane 70:30 then ethyl acetate to give diastereomer 1 (2R)-2-[(S)-(4-chlorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one and (2S)-2-[(R)-(4-chlorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one as a solid (2.64 g) followed by diastereomer 2 (2R)-2-[(R)-(4-chlorophenyl)(hydroxy)methyl]4-benzylmorpholin-3-one and (2S)-2-[(S)-(4-chlorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one as an oil (1.46 g). Diastereomer 1 was recrystallised from ethyl acetate (25 ml) n-hexane (100 ml) to give white needles (2.47 g, 29%)

Workup

  1. customthe reaction mixture was quenched with aqueous ammonium chloride (100 ml)
  2. extractionextracted with ethyl acetate (100 ml)
  3. washThe extracts were washed with 2M aqueous hydrochloric acid (100 ml), brine solution (100 ml)
  4. dry with materialdried over sodium sulphate
  5. filtrationAfter filtration
  6. customthe solution was evaporated
  7. customthe residual oil purified by chromatography on silica eluting with ethyl acetate:hexane 70:30

Sources & evidence

ORD record
ord-8c433c0981fe47038e9ec5febd3da4fb
Source dataset
uspto-grants-2007_11
Patent number
US07294623B2

Reaction notes

Loading…