Potassium Carbonate → (r)-2-(3-Bromo-4-(2-methoxyethyloxy)benzyl)morpholine

HRID 2252992Notes

Reaction equation

HRID 2252992 reaction equation
C([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([Br:22])[CH:16]=2)[CH2:9]1)(OC(C)(C)C)=O.C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][O:32][CH3:33]>CC(C)=O>[Br:22][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][C:18]=1[O:21][CH2:30][CH2:31][O:32][CH3:33])[CH2:14][C@H:10]1[O:11][CH2:12][CH2:13][NH:8][CH2:9]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl etherHCID 67073493N-BOC-(R)-2-(3-bromo-4-hydroxybenzyl)morpholine

Product 1

HCID 11616887(r)-2-(3-Bromo-4-(2-methoxyethyloxy)benzyl)morpholine

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
55 °C

Procedure

N-BOC-(R)-2-(3-bromo-4-hydroxybenzyl)morpholine, example 4, intermediate (a), (70 mg, 0.19 mmo) was dissolved in acetone (1.5 mL) and treated with potassium carbonate (78 mg, 0.56 mmol) and 2-bromoethylmethyl ether (78 mg, 0.56 mmol) was added and the resulting reaction was shaken at 55° C. for 16 hrs. The reaction was filtered and concentrated under a flow of nitrogen. The crude residue was dissolved in tetrahydrofuran (8 mL) with polymer supported diphenylphosphine (0.5 g) and shaken for 4 hrs. The reaction was then filtered and concentrated under a high flow of nitrogen. The crude residue was dissolved in TFA (20% v/v solution in dichloromethane, 2.5 mL) and shaken for 3 hrs at room temperature. The reaction mixture was added directly to an SCX-2 column (2 g) and washed with dichloromethane (2 mL×2) and methanol (2 mL×2). The SCX-2 column was then washed with ammonia (2N in methanol, 3×2 mL). Combined ammonia washes were concentrated in vacuo to yield the desired morpholine example 36 as a colorless oil (31 mg).

Workup

  1. additionwas added
  2. customthe resulting reaction
  3. filtrationThe reaction was filtered
  4. concentrationconcentrated under a flow of nitrogen
  5. dissolutionThe crude residue was dissolved in tetrahydrofuran (8 mL) with polymer
  6. stirringshaken for 4 hrs
  7. filtrationThe reaction was then filtered
  8. concentrationconcentrated under a high flow of nitrogen
  9. dissolutionThe crude residue was dissolved in TFA (20% v/v solution in dichloromethane, 2.5 mL)
  10. stirringshaken for 3 hrs at room temperature
  11. additionThe reaction mixture was added directly to an SCX-2 column (2 g)
  12. washwashed with dichloromethane (2 mL×2) and methanol (2 mL×2)
  13. washThe SCX-2 column was then washed with ammonia (2N in methanol, 3×2 mL)
  14. concentrationCombined ammonia washes were concentrated in vacuo

Sources & evidence

ORD record
ord-85bb5abd5a5d45f08559f5fad3c776ff
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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