Methanol → HCID 21192615, compound

HRID 1068032Notes

Reaction equation

HRID 1068032 reaction equation
[NH2:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[CH3:15][OH:16]>>[N:7]1([CH2:6][C:5]2[CH:13]=[CH:14][C:2]([NH:1][CH:2]3[CH2:3][CH2:4][O:16][CH2:15][CH2:14]3)=[CH:3][CH:4]=2)[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1

Participants

3

Reactant 2

HCID 887MethanolHCID 7768514-(Morpholinomethyl)aniline

Product 1

HCID 21192615HCID 21192615, compound

Procedure

A flask containing 4-(4-aminobenzyl)morpholine from Preparation No. 22 (0.48 g) is treated with methanol (5 mL) and a few dozen dry molecular sieves (3 Å). The mixture is treated with acetic acid (1 mL) and terahydro-4H-pyran-4-one (0.24 mL). After 1 hour, the mixture is carefully treated with sodium cyanoborohydride (0.6 g) and heated to reflux under an argon atmosphere. After 1 hour, the mixture is cooled to room temperature and filtered with methanol washes. The filtrate is diluted with diethyl ether and washed with aqueous sodium hydroxide (2N). The aqueous is back-extracted with dichloromethane. The combined organic layers are washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue is flash column chromatographed on silica eluting with 2% to 5% methanol in dichloromethane. The product-containing fractions are combined and evaporated to afford 0.34 g of N-[4-(4-morpholinylmethyl)phenyl]tetrahydro-2H-pyran-4-amine as a white solid.

Workup

  1. customfrom Preparation No
  2. customa few dozen dry molecular sieves (3 Å)
  3. additionThe mixture is treated with acetic acid (1 mL) and terahydro-4H-pyran-4-one (0.24 mL)
  4. additionthe mixture is carefully treated with sodium cyanoborohydride (0.6 g)
  5. temperatureheated
  6. temperatureto reflux under an argon atmosphere
  7. waitAfter 1 hour
  8. filtrationfiltered with methanol washes
  9. additionThe filtrate is diluted with diethyl ether
  10. washwashed with aqueous sodium hydroxide (2N)
  11. extractionThe aqueous is back-extracted with dichloromethane
  12. washThe combined organic layers are washed with brine
  13. dry with materialdried over sodium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customchromatographed on silica eluting with 2% to 5% methanol in dichloromethane
  16. customevaporated

Sources & evidence

ORD record
ord-29b2668ee9e149d4afd3ab109c4c225e
Source dataset
uspto-grants-2001_06
Patent number
US06248739B1

Reaction notes

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