Ethyl Acetate → N-benzyl-2-(2-fluoro-3-methyl-benzyl)-morpholine

HRID 2253014Notes

Reaction equation

HRID 2253014 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21]O)[CH:16]=2)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH2:23]([N:30]1[CH2:35][CH2:34][O:33][CH:32]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[C:38]=2[F:44])[C:31]1=O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+].C(OCC)(=O)C>O1CCCC1>[C:1]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH:21]=[CH:38][C:37]3[CH:42]=[N:30][CH:31]=[CH:32][CH:36]=3)[CH:16]=2)[CH2:9]1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2].[CH2:23]([N:30]1[CH2:35][CH2:34][O:33][CH:32]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[C:38]=2[F:44])[CH2:31]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 9357Potassium Sodium TartrateHCID 67073062N-Boc-(R)-2-(3-(hydroxymethyl)benzyl)morpholineHCID 67073236N-benzyl-2-(2-Fluoro-3-methyl-benzyl)-morpholin-3-one

Product 2

HCID 67073026N-benzyl-2-(2-fluoro-3-methyl-benzyl)-morpholineHCID 67073511N-Boc-(R)-2-(3-(2-(3-pyridinyl)vinyl)-benzyl)morpholine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
23 °C

Procedure

To a solution of intermediate (b), N-benzyl-2-(2-Fluoro-3-methyl-benzyl)-morpholin-3-one (275 mg, 0.876 mmol) in tetrahydrofuran (10 mL) at 0° C. was added BH3 (1M in tetrahydrofuran, 2.63 mL, 2.63 mmol). The mixture was stirred at 23° C. for 1 h then heated to reflux for 18 h, cooled to 23° C. and stirred vigorously with Rochelle's salt solution (15 mL) for 1.5 h. Ethyl acetate (30 mL) was added and stirring continued for 1.5 h. The organic phase was separated, dried (Na2SO4) and concentrated affording intermediate (a), N-benzyl-2-(2-fluoro-3-methyl-benzyl)-morpholine, as a pale yellow oil (190 mg, 73%).

Workup

  1. temperaturethen heated
  2. temperatureto reflux for 18 h
  3. temperaturecooled to 23° C.
  4. stirringstirring
  5. waitcontinued for 1.5 h
  6. customThe organic phase was separated
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-cfc18c548e40431cbd4e103daca7a5dd
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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