Toluene → HCID 58689699, compound

HRID 2252970Notes

Reaction equation

HRID 2252970 reaction equation
[OH-].[Na+].Cl[CH2:4][C@H:5]([OH:15])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][CH3:14].S(O)(O)(=O)=O.[NH2:21][CH2:22][CH3:23].C1(C)C=CC=CC=1>O.CO>[CH3:14][O:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[CH2:6][C@H:5]1[O:15][CH2:23][CH2:22][NH:21][CH2:4]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 14798Sodium Hydroxide2×HCID 19907958Sulfuric acid--ethanamine (1/1)HCID 58689703HCID 58689703, compound

Product 1

HCID 58689699HCID 58689699, compoundYield 97.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
40 °C

Procedure

Powdered sodium hydroxide (7.2 g, 180 mmol) was dissolved in water (15 mL). The solution was allowed to cool to ambient temperature before addition of intermediate (a) (R)-1-chloro-3-(2-methoxyphenyl)-2-propanol(6.0 g, 30.0 mmol) in methanol (20 mL+2×5 mL washes) via dropping funnel. After stirring for 5 mins 2-aminoethane hydrogen sulfate (16.9 g, 120 mmol) was added in portions over 5 mins and the reaction mixture heated to 40° C. After 2 hrs, toluene (75 mL) and powdered sodium hydroxide (7.2 g, 180 mmol) were added and the reaction heated to 65° C. and stirred for 17 hrs. The mixture was cooled, diluted with water (300 mL) and extracted with toluene (2×150 mL). The combined organics were washed with water (slowly separating emulsion obtained) and brine, dried (Na2SO4) and concentrated under reduced pressure to afford the crude product as a pale yellow oil (5.21 g). Purification by column chromatography (silica: ethyl acetate/ethanol/triethylamine, 79/20/1 ratio) afforded intermediate (d), (R)-2-(2-methoxybenzyl)morpholine as a colorless oil (6.04 g, 50% yield).

Workup

  1. additionwas added in portions over 5 mins
  2. temperaturethe reaction heated to 65° C.
  3. temperatureThe mixture was cooled
  4. extractionextracted with toluene (2×150 mL)
  5. washThe combined organics were washed with water (
  6. customslowly separating emulsion
  7. customobtained) and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customto afford the crude product as a pale yellow oil (5.21 g)
  11. customPurification by column chromatography (silica: ethyl acetate/ethanol/triethylamine, 79/20/1 ratio)

Sources & evidence

ORD record
ord-d5b2c320e3414ae8b2651218b2c6529b
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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