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

HRID 419386Notes

Reaction equation

HRID 419386 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-AlHCID 59452664(3R)-5-oxo-N,4-bis(phenylmethyl)-3-morpholinecarboxamide

Product 1

HCID 594527491-phenyl-N-{[(3S)-4-(phenylmethyl)-3-morpholinyl]methyl}methanamineYield 94.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

(3R)-5-oxo-N,4-bis(phenylmethyl)-3-morpholinecarboxamide (5.09 g, 15.6 mmol) in toluene (50 mL) cooled to 0° C. Red-Al® (35.0 mL, 7 mL per g carboxamide) added via addition funnel. The ice bath was removed after 2 or 3 mL Red-Al® was added. The reaction was heated at 50° C. overnight. The reaction was cooled to 0° C. and quenched slowly with 1N NaOH (50 mL) followed by diethyl ether (50 mL). The organic layer was washed with 1N NaOH (50 mL), the combined aqueous layer was back extracted with toluene (50 mL) and diethyl ether (50 mL) and dried over MgSO4 to provide the title compound of step D (4.35 g, 14.7 mmol, 94%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.97 (br. s., 1H), 2.06 (ddd, J=12.0, 9.2, 3.4 Hz, 1H), 2.33-2.41 (m, 1H), 2.43-2.48 (m, 1H), 2.54-2.66 (m, 2H), 3.13 (d, J=13.6 Hz, 1H), 3.32-3.39 (m, 1H), 3.42 (dd, J=11.2, 8.2 Hz, 1H), 3.53 (dt, J=11.1, 3.5 Hz, 1H), 3.57-3.62 (m, 2H), 3.70 (dd, J=11.1, 3.0 Hz, 1H), 3.93 (d, J=13.6 Hz, 1H), 7.16-7.27 (m, 10H).

Workup

  1. customThe ice bath was removed after 2 or 3 mL Red-Al®
  2. additionwas added
  3. temperatureThe reaction was cooled to 0° C.
  4. customquenched slowly with 1N NaOH (50 mL)
  5. washThe organic layer was washed with 1N NaOH (50 mL)
  6. extractionthe combined aqueous layer was back extracted with toluene (50 mL) and diethyl ether (50 mL)
  7. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-d24251f530e24db4bd5cdb6105ade199
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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