Water → (S)-4-Benzyl-2-(4-fluorophenyl)morpholine

HRID 880231Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][C@H:12]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[O:11][CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[CH2:1]([N:8]1[CH2:9][CH2:10][O:11][C@@H:12]([C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 20 °C

Procedure

Under a nitrogen atmosphere, drop-wise add a solution of (6S)-4-benzyl-6-(4-fluorophenyl) morpholin-3-one (625 g, 2.19 mol) in THF (22 L) to lithium aluminum hydride in THF (1M in THF, 5.0 L, 5 mol) while maintaining the temperature at 20° C. Heat the mixture to 70° C. and stir for 1.5 h. Cool the mixture to 0° C. and add H2O (200 mL) to quench the reaction, followed by aqueous NaOH (4 M, 1.25 L), then add more H2O (600 mL). Stir the resulting mixture for 30 min; filter; and rinse the solid with EtOAc (10 L). Collect the filtrate and concentrate it under reduced pressure to provide the title compound (561 g, 94%). MS (m/z): 272 (M+1).

Workup

temperatureHeat the mixture to 70° C.
temperatureCool the mixture to 0° C.
customto quench
customthe reaction
stirringStir the resulting mixture for 30 min
filtrationfilter
washand rinse the solid with EtOAc (10 L)
customCollect the filtrate
concentrationconcentrate it under reduced pressure

Sources & evidence

ORD record: ord-77da1c77cef0431d9c75652eb0956b02
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993568B2

Reaction notes

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