Ammonium Chloride → HCID 57634205, compound

HRID 661114Notes

Reaction equation

HRID 661114 reaction equation
[CH2:1]([N:8]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C@@H:9]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=1)[CH:10]=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:30][Mg]Br.[Cl-].[NH4+]>CCOCC>[CH2:23]([N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C@@H:9]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=1)[C@H:10]([OH:11])[CH3:30])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 57634167(αS)-α-[Bis(phenylmethyl)amino]-4-(trifluoromethyl)benzenepropanalHCID 178418573HCID 178418573, compound

Product 1

HCID 57634205HCID 57634205, compoundYield 66.1%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

Ether (100 mL) was added to a 500 mL round-bottom flask containing (S)-2-(dibenzylamino)-3-(4-(trifluoromethyl)phenyl)propanal (4.51 g, 11.3 mmol). The mixture was cooled to −78° C., and methylmagnesium bromide (3.16 M ether, 35.9 mL, 113 mmol) was added dropwise over 15 minutes. After 5 hours, ammonium chloride (50 mL) was added dropwise, and the mixture was warmed to room temperature. The mixture was extracted with EtOAc (2×500 mL), washed with brine (250 mL), dried over sodium sulfate, and purified by chromatography through a 300 g column eluting with a gradient of 0% to 70% EtOAc in hexane, to provide (2R,3S)-3-(dibenzylamino)-4-(4-(trifluoromethyl)phenyl)butan-2-ol (3.09 g, 65.9% yield) as a yellow oil. LCMS (ES+) m/z=414.3 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 1.23-1.28 (m, 3H) 2.84-2.94 (m, 2H) 3.08 (dd, J=12.81, 6.36 Hz, 1H) 3.66-3.76 (m, 4H) 4.03 (dt, J=10.66, 6.41 Hz, 1H) 7.15-7.28 (m, 12H) 7.51 (d, J=8.02 Hz, 2H).

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. extractionThe mixture was extracted with EtOAc (2×500 mL)
  3. washwashed with brine (250 mL)
  4. dry with materialdried over sodium sulfate
  5. custompurified by chromatography through a 300 g column
  6. washeluting with a gradient of 0% to 70% EtOAc in hexane

Sources & evidence

ORD record
ord-e5f2a567436343c3a621c00bf8af1aef
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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