(3S)-4-Benzyl-3-(4-fluorophenyl)morpholin-2-one → (2R,3S)-4-Benzyl-3-(4-fluorophenyl)-2-hydroxy-2-(prop-2-enyl)morpholine

HRID 1421859Notes

Reaction equation

HRID 1421859 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][C:10](=[O:14])[C@@H:9]1[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:22]([Mg]Cl)[CH:23]=[CH2:24]>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][C@:10]([OH:14])([CH2:24][CH:23]=[CH2:22])[C@@H:9]1[C:15]1[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 10891424(3S)-4-Benzyl-3-(4-fluorophenyl)morpholin-2-oneHCID 178418473HCID 178418473, compound

Product 1

HCID 53937215(2R,3S)-4-Benzyl-3-(4-fluorophenyl)-2-hydroxy-2-(prop-2-enyl)morpholine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(3S)-4-Benzyl-3-(4-fluorophenyl)-2-morpholinone (see International Patent Specification No. WO 95/18124) (13.6 g, 47.6 mmol) was dissolved in anhydrous tetrahydrofuran (200 ml) and cooled to below -70° C. under an inert atmosphere. Allyl magnesium chloride (26.2 ml of a 2.0M solution in tetrahydrofuran; 52.4 mmol) was added dropwise over 15 minutes, maintaining the temperature below -70° C. After 30 minutes, the reaction was quenched by the addition of a saturated solution of ammonium chloride and allowed to warm to room temperature. The resulting suspension was extracted with ethyl acetate (3×100 ml), and the combined organic extracts dried (MgSO4) and concentrated in vacuo to yield the title compound in ~3:1 mixture of the lactols as a light yellow oil (15.3 g, 98%), which was used without further purification. m/z (ES+) 328 (M+1, 22%), 310 (M--OH, 61), 269 (100).

Workup

  1. temperaturecooled to below -70° C. under an inert atmosphere
  2. addition52.4 mmol) was added dropwise over 15 minutes
  3. temperaturemaintaining the temperature below -70° C
  4. customthe reaction was quenched by the addition of a saturated solution of ammonium chloride
  5. extractionThe resulting suspension was extracted with ethyl acetate (3×100 ml)
  6. dry with materialthe combined organic extracts dried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-589c91cec7654ecb8c1b1082c0224ca4
Source dataset
uspto-grants-2000_06
Patent number
US06080740

Reaction notes

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