Formaldehyde → (2S)-2-(4-(N-methyl-N-((3R)-tetrahydrofuran-3-yl)amino)phenyl)-4-((1R)-1-phenylethyl)morpholine

HRID 1091366Notes

Reaction equation

HRID 1091366 reaction equation
[C:1](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]1([C@H:21]([N:23]2[CH2:28][CH2:27][O:26][C@@H:25]([C:29]3[CH:34]=[CH:33][C:32]([NH:35][C@@H:36]4[CH2:40][CH2:39][O:38][CH2:37]4)=[CH:31][CH:30]=3)[CH2:24]2)[CH3:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C=O>ClC(Cl)C>[CH3:1][N:35]([C:32]1[CH:33]=[CH:34][C:29]([C@@H:25]2[O:26][CH2:27][CH2:28][N:23]([C@@H:21]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH3:22])[CH2:24]2)=[CH:30][CH:31]=1)[C@@H:36]1[CH2:40][CH2:39][O:38][CH2:37]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 665944544-((1R)-1-phenylethyl)-(2S)-2-(4-(N-((3R)-tetrahydrofuran-3-yl)amino)phenyl)morpholine

Product 1

HCID 66594800(2S)-2-(4-(N-methyl-N-((3R)-tetrahydrofuran-3-yl)amino)phenyl)-4-((1R)-1-phenylethyl)morpholineYield 100%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (2.4 g, 11.3 mmol) was added to a solution of 4-((1R)-1-phenylethyl)-(2S)-2-(4-(N-((3R)-tetrahydrofuran-3yl)amino)phenyl)-morpholine (1.3 g, 3.69 mmol) and formalin (35%, 1.6 g, 18.6 mmol) in dichloroethane (50 mL) at room temperature. After stirring for 2 hours, the resulting suspension was partitioned between ethyl acetate and 1 N sodium hydroxide. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting 5-10% methanol in chloroform to furnish (2S)-2-(4-(N-methyl-N-((3R)-tetrahydrofuran-3-yl)amino)phenyl)-4-((1R)-1-phenylethyl)morpholine (1.35 g, 100%) as a pale yellow oil.

Workup

  1. customthe resulting suspension was partitioned between ethyl acetate and 1 N sodium hydroxide
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluting 5-10% methanol in chloroform

Sources & evidence

ORD record
ord-cfefbc3c93654d68b79b99afd7f8bcbd
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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