3-Fluorobenzaldehyde → HCID 58610198, compound

HRID 1592832Notes

Reaction equation

HRID 1592832 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH2:9]([N:16]1[CH2:21][CH2:20][O:19][CH2:18][C:17]1=[O:22])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[F:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH:27]=[O:28]>O1CCCC1>[F:23][C:24]1[CH:25]=[C:26]([C@H:27]([OH:28])[C@H:18]2[O:19][CH2:20][CH2:21][N:16]([CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:17]2=[O:22])[CH:29]=[CH:30][CH:31]=1.[F:23][C:24]1[CH:25]=[C:26]([C@@H:27]([OH:28])[C@@H:18]2[O:19][CH2:20][CH2:21][N:16]([CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:17]2=[O:22])[CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 3

HCID 680093-FluorobenzaldehydeHCID 2724682Lithium diisopropylamideHCID 122940874-Benzylmorpholin-3-one

Product 2

HCID 58610168HCID 58610168, compoundHCID 58610198HCID 58610198, compoundYield 92.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

A solution of lithium diisopropylamide (2M in heptane, 16.9 ml) was added dropwise over 15 min to a stirred solution of 4-benzyl-morpholin-3-one (5.0 g, 26 mmol) and 3-fluorobenzaldehyde (3.55 g, 28.6 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 (2×50 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)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one and (2S)-2-[(R)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one as a solid (3.8 g) followed by diastereomer 2 (2R)-2-[(R)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one and (2S)-2-[(S)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one as an oil (2.13 g). Diastereomer 1 was recrystallised from ethyl acetate (25 ml) n-hexane (100 ml) to give white needles (2.62 g, 32%).

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 (2×50 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-b427559326f348088fa29ad96d88e14a
Source dataset
uspto-grants-2007_11
Patent number
US07294623B2

Reaction notes

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