Hydrochloric Acid → (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

HRID 14284Notes

Reaction equation

HRID 14284 reaction equation
C(OC(=O)[NH:7][CH:8]([CH2:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=1)[CH:9]([OH:21])[CH2:10][NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH3:20])[CH:14]=1)(C)(C)C.[ClH:32]>O1CCOCC1>[ClH:32].[ClH:32].[NH2:7][C@@H:8]([CH2:22][C:23]1[CH:24]=[C:25]([F:30])[CH:26]=[C:27]([F:29])[CH:28]=1)[C@H:9]([OH:21])[CH2:10][NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH3:20])[CH:14]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57487425HCID 57487425, compound

Product 1

HCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

The slurry of [1-(3,5-difluorobenzyl)-3-(3-ethylbenzylamino)-2-hydroxypropyl]-carbamic acid tert-butyl ester (5.25 g, 0.012 m) in anhydrous dioxane (20 ml) was stirred (magnetic bar) at RT under nitrogen atmosphere in an 250 ml round-bottom flask, immersed in a cold water bath. The solution of hydrogen chloride in dioxane (4M, 32 ml) was added in one portion. The reaction mixture, initially homogenous, became a thick slurry within ca. 20 min. Mixture was stirred for 70 min, and was monitored by the TLC (silica gel plates, 5×10 cm, eluted with ethyl acetate-methanol 95:5 mixture). Ethyl ether (100 ml) was added, precipitated product was filtered off and rinsed with ether (2×50 ml). The filter cake was air-dried for 1 hour then placed in an vacuum oven at 35° C. and the oven evacuated (5 torr). Product was dried to constant mass for 7 hours. Yield was 5.24 g. LC-MS (m/e): 335 (M+1); purity: 100% (254 nm).

Workup

  1. customimmersed in a cold water bath
  2. customwithin ca. 20 min
  3. washwas monitored by the TLC (silica gel plates, 5×10 cm, eluted with ethyl acetate-methanol 95:5 mixture)
  4. additionEthyl ether (100 ml) was added
  5. customprecipitated product
  6. filtrationwas filtered off
  7. washrinsed with ether (2×50 ml)
  8. customThe filter cake was air-dried for 1 hour
  9. customthen placed in an vacuum oven at 35° C.
  10. customthe oven evacuated (5 torr)
  11. customProduct was dried to constant mass for 7 hours

Sources & evidence

ORD record
ord-b4255997115b4b26aa2964641c362fc4
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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