Red-Al → 1-phenyl-N-{[(3S)-4-(phenylmethyl)-3-morpholinyl]methyl}methanamine

HRID 1366411Notes

Reaction equation

HRID 1366411 reaction equation
O=[C:2]1[N:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C@@H:6]([C:15]([NH:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=O)[CH2:5][O:4][CH2:3]1.COCCO[AlH2-]OCCOC.[Na+]>C1(C)C=CC=CC=1>[C:19]1([CH2:18][NH:17][CH2:15][C@H:6]2[CH2:5][O:4][CH2:3][CH2:2][N:7]2[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

4

Reactant 2

HCID 16684438Red-Al2×HCID 59452664(3R)-5-oxo-N,4-bis(phenylmethyl)-3-morpholinecarboxamide

Product 1

HCID 594527491-phenyl-N-{[(3S)-4-(phenylmethyl)-3-morpholinyl]methyl}methanamine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a 0° C. solution of (3R)-5-oxo-N,4-bis(phenylmethyl)-3-morpholinecarboxamide (assumed 96.07 g, 296.2 mmol) in PhMe (750 mL) was added Red-Al (65% w/w in PhMe, 645 mL) via addition funnel. After approximately 50 mL of Re-Al had been added, the resulting mixture was warmed to room temperature, and the remainder of the Red-Al was then added over 30 min. The mixture was then heated at 50° C. and stirred overnight. The solution was cooled to 0° C., and the reaction was quenched by the slow dropwise addition of 1 N aqueous NaOH (50 mL). An additional portion of 1 N aqueous NaOH (500 mL) was then added, followed by Et2O (200 mL). The phases were separated, and the organic phase was washed with fresh 1 N aqueous NaOH (400 mL). The combined aqueous phase was extracted with fresh 4:1 PhMe-Et2O (250 mL), and the combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 1-phenyl-N-{[(3S)-4-(phenylmethyl)-3-morpholinyl]methyl}methanamine as a yellow oil that was used without further purification. LCMS: (M+H)+: 297.1.

Workup

  1. additionvia addition funnel
  2. additionAfter approximately 50 mL of Re-Al had been added
  3. temperatureThe mixture was then heated at 50° C.
  4. temperatureThe solution was cooled to 0° C.
  5. customthe reaction was quenched by the slow dropwise addition of 1 N aqueous NaOH (50 mL)
  6. additionAn additional portion of 1 N aqueous NaOH (500 mL) was then added
  7. customThe phases were separated
  8. washthe organic phase was washed with fresh 1 N aqueous NaOH (400 mL)
  9. extractionThe combined aqueous phase was extracted with fresh 4:1 PhMe-Et2O (250 mL)
  10. dry with materialthe combined organic phase was dried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-595e549416d04fc699e40a7e5a9958bb
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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