Formaldehyde → (S)-2-(4-(N-cyclohexyl-N-methylamino)phenyl)-4-((R)-1-phenylethyl)morpholine

HRID 424421Notes

Reaction equation

HRID 424421 reaction equation
[CH:1]1([NH:7][C:8]2[CH:13]=[CH:12][C:11]([C@@H:14]3[O:19][CH2:18][CH2:17][N:16]([C@@H:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH3:21])[CH2:15]3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C=O.[C:30](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH:1]1([N:7]([C:8]2[CH:9]=[CH:10][C:11]([C@@H:14]3[O:19][CH2:18][CH2:17][N:16]([C@@H:20]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH3:21])[CH2:15]3)=[CH:12][CH:13]=2)[CH3:30])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 66703919(S)-2-(4-(cyclohexylamino)phenyl)-4-((R)-1-phenylethyl)morpholine

Product 1

HCID 66703943(S)-2-(4-(N-cyclohexyl-N-methylamino)phenyl)-4-((R)-1-phenylethyl)morpholineYield 100.5%

Procedure

To a solution of (S)-2-(4-(cyclohexylamino)phenyl)-4-((R)-1-phenylethyl)morpholine (6.95 g, 19.1 mmol) and formalin (35%, 8.18 ml, 95.4 mmol) was added sodium triacetoxyborohydride (12.1 g, 57.2 mmol) at room temperature. After stirring for 30 minutes, 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 5-20% ethyl acetate in hexane to furnish (2S)-2-(4-(N-cyclohexyl-N-methylamino)phenyl)-4-((1R)-1-phenylethyl)morpholine (7.27 g, quant.) 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 5-20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-6dc8e6a5099042418aa90ce6cae756c3
Source dataset
uspto-grants-2012_01
Patent number
US08106045B2

Reaction notes

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