Isopropanol → tert-butyl (1S)-1-(3,5-difluorobenzyl)-3-[(3-methoxybenzyl)amino]-2-oxopropylcarbamate

HRID 1783222Notes

Reaction equation

HRID 1783222 reaction equation
Br[CH2:2][C:3](=[O:22])[C@@H:4]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]([F:13])[CH:7]=1.[C@@H:23]1([NH2:33])[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)CCC1.[CH:34]([OH:37])(C)C>>[F:13][C:8]1[CH:7]=[C:6]([CH:11]=[C:10]([F:12])[CH:9]=1)[CH2:5][C@H:4]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:3](=[O:22])[CH2:2][NH:33][CH2:23][C:32]1[CH:31]=[CH:30][CH:29]=[C:28]([O:37][CH3:34])[CH:27]=1

Participants

4

Reactant 3

HCID 3776IsopropanolHCID 70580741-Aminotetralin, (S)-HCID 57484758HCID 57484758, compound2×

Product 1

HCID 86585851tert-butyl (1S)-1-(3,5-difluorobenzyl)-3-[(3-methoxybenzyl)amino]-2-oxopropylcarbamate

Procedure

tert-butyl (1S)-3-bromo-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate (III, EXAMPLE 1, 1 equivalent) is dissolved in isopropanol and treated with 3-methoxybenzylamine (VI, 5 equivalents). The reaction is heated at reflux for 2 hours and monitored by TLC for disappearance of the ketone (III). Upon completion, the reaction is concentrated to dryness under reduced pressure and partitioned between equal parts water and ethyl acetate. The organic phase is extracted, washed two additional times with water, then saline, then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude material is purified by column chromatography on silica gel to give the title compound.

Workup

  1. temperatureThe reaction is heated
  2. temperatureat reflux for 2 hours
  3. concentrationUpon completion, the reaction is concentrated to dryness under reduced pressure
  4. custompartitioned between equal parts water and ethyl acetate
  5. extractionThe organic phase is extracted
  6. washwashed two additional times with water
  7. dry with materialsaline, then dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material is purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-e6b54782d3d54a7482681e2989745206
Source dataset
uspto-grants-2009_03
Patent number
US07498436B2

Reaction notes

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