Water → HCID 67165303, compound

HRID 553307Notes

Reaction equation

HRID 553307 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][C:10]1[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=1)[CH:13]=O.[CH3:18][O:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH2:22][NH2:23].O.CCCC(C)C.CCOC(C)=O>C1(C)C=CC=CC=1.CC1C=CC(S(O)(=O)=O)=CC=1>[CH3:18][O:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH2:22][NH:23][CH2:13][C:12]1[CH:15]=[CH:16][CH:17]=[C:10]([CH2:9][CH2:8][O:7][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)[CH:11]=1

Participants

7

Reactant 4

HCID 962WaterHCID 812922-MethoxybenzylamineHCID 21882781Isohexane ethyl acetateHCID 866183253-[2-(Tetrahydropyran-2-yloxy)-ethyl]-benzaldehyde

Product 1

HCID 67165303HCID 67165303, compoundYield 42.8%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-benzaldehyde (10 g) and 2-methoxybenzylamine (6 g) in toluene (150 mL) was added TsOH (100 mg). The mixture was heated at reflux in a Dean-Stark apparatus for a couple of hours. About 1 mL water was displaced. The reaction was checked by TLC, iso-hexane/EtOAc (4/1, Rf ˜0.5). The mixture was cooled and washed with aqueous bicarbornate, then concentrated in vacuo. The residue was azeotroped twice with toluene and was taken up in ethanol (150 ml). The solution was cooled to 0° C. and sodium borohydride (1.65 g) was added slowly. The reaction was left to warm to room temperature and was stirred overnight. Water was added (150 mL) and ethanol removed under vacuum. The residue was partitioned between aqueous bicarbonate and ethyl acetate. The organic layers were dried over sodium sulfate and concentrated in vacuo to give a yellow oil (6.5 g). The material was used in the next step without further purification.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux in a Dean-Stark apparatus for a couple of hours
  3. temperatureThe mixture was cooled
  4. washwashed with aqueous bicarbornate
  5. concentrationconcentrated in vacuo
  6. customThe residue was azeotroped twice with toluene
  7. additionsodium borohydride (1.65 g) was added slowly
  8. waitThe reaction was left
  9. temperatureto warm to room temperature
  10. additionWater was added (150 mL) and ethanol
  11. customremoved under vacuum
  12. customThe residue was partitioned between aqueous bicarbonate and ethyl acetate
  13. dry with materialThe organic layers were dried over sodium sulfate
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5c234c5bb0b645719f9827ddac0fcf68
Source dataset
uspto-grants-2011_05
Patent number
US07951954B2

Reaction notes

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