Tetrahydrofuran → 4-Benzylmorpholin-3-one

HRID 30321Notes

Reaction equation

HRID 30321 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][C:9]1=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[CH2:23]1[CH2:27][O:26][CH2:25][CH2:24]1>>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH:25]([CH:24]2[CH2:23][CH2:27]2)[OH:26])[C:9]1=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][C:9]1=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 2724682Lithium diisopropylamideHCID 122940874-Benzylmorpholin-3-one

Product 2

HCID 122940874-Benzylmorpholin-3-oneHCID 597892904-Benzyl-2-(cyclopropyl(hydroxy)methyl)morpholin-3-one

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-benzyl-morpholin-3-one (9.5 g, 50 mmol) in THF (200 mL) is added lithium diisopropylamide (2M solution in THE, 27 mL, 54 mmol, 1.1 eq) dropwise over 20 minutes at −78° C. followed by slow addition of cyclopropyl methylaldehyde (3.85 mL, 55 mmol, 1.1 eq). After stirring at −78° C. for one hour the reaction mixture is allowed to warm to room temperature and stirred for another 6 hours. The reaction is quenched by addition of EtOAc and brine. The aqueous layer is extracted with EtOAc, the combined organic layers are dried over magnesium sulphate and reduced in vacuo. Purification using automated column chromatography (DCM/MeOH, 100/0 to 85/15 [v/v]) gives 75 in 70% purity with 4-benzyl-morpholin-3-one as the major impurity. This product is directly used in the next step. MW 261.32; C15H19NO3; LCMS (6 min method) m/z 261.32 [M+H]+, RT 2.23

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for another 6 hours
  3. customThe reaction is quenched by addition of EtOAc and brine
  4. extractionThe aqueous layer is extracted with EtOAc
  5. dry with materialthe combined organic layers are dried over magnesium sulphate
  6. customPurification

Sources & evidence

ORD record
ord-d1dcd993d31a40b9b1ec99ff3b72a5e0
Source dataset
uspto-grants-2008_09
Patent number
US07423037B2

Reaction notes

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