1,4-Anhydroerythritol → 4-((R)-1-Benzyl-pyrrolidin-3-yl)-morpholine

HRID 1011881Notes

Reaction equation

HRID 1011881 reaction equation
[CH2:1]1[O:7][CH2:6][C@@H:4](O)[C@H:2]1O.[Na].[CH2:9]([N:16]1[CH2:20][CH2:19][C@@H:18]([NH2:21])[CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C([BH3-])#N.[Na+]>O.C(#N)C>[CH2:9]([N:16]1[CH2:20][CH2:19][C@@H:18]([N:21]2[CH2:4][CH2:6][O:7][CH2:1][CH2:2]2)[CH2:17]1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 6417731,4-AnhydroerythritolHCID 1519354(3R)-1-benzylpyrrolidin-3-amineHCID 5003444Sodium cyanoborohydrideHCID 5360545Sodium

Product 1

HCID 590796834-((R)-1-Benzyl-pyrrolidin-3-yl)-morpholineYield 28%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent3×

Procedure

To a solution of 1,4-anhydroerythritol (1.9 g, 18 mmol) in water (10 ml) was added sodium periodiate (0.7 g, 18 mmol) and the reaction stirred for 16 h. Acetonitrile (10 ml) was added to the mixture and the reaction was filtered to remove precipitated salts. (R)-1-benzyl-pyrrolidin-3-ylamine (1.0 g, 6 mmol) was added as a solution in acetonitrile (5 ml) to the filtrate, followed by sodium cyanoborohydride (1.1 g, 18 mmol). The reaction was stirred for 10 minutes after which time the reaction the acetonitrile removed by evaporation, the mixture made basic by addition of NaHCO3, and repeatedly extracted with CH2Cl2. The combined organic extracts were dried (Na2SO4) and concentrated. Purification by flash column chromatography (CH2Cl2:MeOH 9:1) afforded the title product (0.4 g, 28%) as a brown gum. MS: 247.2 (MH+).

Workup

  1. filtrationthe reaction was filtered
  2. customto remove
  3. customprecipitated salts
  4. stirringThe reaction was stirred for 10 minutes after which time
  5. customremoved by evaporation
  6. additionthe mixture made basic by addition of NaHCO3
  7. extractionrepeatedly extracted with CH2Cl2
  8. dry with materialThe combined organic extracts were dried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification by flash column chromatography (CH2Cl2:MeOH 9:1)

Sources & evidence

ORD record
ord-84a04fbcc55346c6bd3729f14fa635c9
Source dataset
uspto-grants-2011_07
Patent number
US07977358B2

Reaction notes

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