Toluene → HCID 11543494, compound

HRID 2252973Notes

Reaction equation

HRID 2252973 reaction equation
[OH-].[Na+].Cl[CH2:4][C@H:5]([OH:18])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([C:14]([F:17])([F:16])[F:15])[CH:8]=1.S(O)(O)(=O)=O.[NH2:24][CH2:25][CH3:26].C1(C)C=CC=CC=1>O.CO>[F:13][C:10]1[CH:11]=[CH:12][C:7]([CH2:6][C@H:5]2[O:18][CH2:26][CH2:25][NH:24][CH2:4]2)=[CH:8][C:9]=1[C:14]([F:17])([F:16])[F:15]

Participants

7

Reactant 4

HCID 1140TolueneHCID 14798Sodium Hydroxide2×HCID 19907958Sulfuric acid--ethanamine (1/1)HCID 58689706HCID 58689706, compound

Product 1

HCID 11543494HCID 11543494, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

Powdered sodium hydroxide (3.36 g, 84 mmol) was dissolved in water (5.6 mL) and cooled to room temperature. Intermediate (d) (R)-1-chloro-3-(4-fluoro-3-trifluoromethylphenyl)-2-propanol (assumed 13 mmol) was added as a solution in methanol (13.3 mL in total) and the mixture stirred for 5 minutes at room temperature. 2-aminoethane hydrogen sulfate (7.90 g, 56 mmol) was added in one portion and the resultant mixture warmed to 40° C. (bath temperature) for 2 hrs. Toluene (35 mL) and sodium hydroxide (powdered 3.36 g, 84 mmol) were added and the reaction heated at 65° C. (bath temperature) for 18 hrs, with vigorous stirring. The reaction was allowed to cool to room temperature and poured into water (80 mL), layers separated and the aqueous layer extracted with ethyl acetate (40 mL×2). Combined organic layers were washed with brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica; triethylamine/ethanol ethanol/ethyl acetate, 1/20/79 ratio) yielded the desired intermediate (c), (R)-2-(4-fluoro-3-trifluoromethylbenzyl)morpholine, as yellow oil (2.34 g).

Workup

  1. temperaturethe reaction heated at 65° C. (bath temperature) for 18 hrs
  2. temperatureto cool to room temperature
  3. customseparated
  4. extractionthe aqueous layer extracted with ethyl acetate (40 mL×2)
  5. washCombined organic layers were washed with brine (30 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (silica; triethylamine/ethanol ethanol/ethyl acetate, 1/20/79 ratio)

Sources & evidence

ORD record
ord-f5910e2dd4874be09e9df02a9e3caf30
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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