Boron tribromide → 2-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-3,3,3-trifluoro-2-hydroxypropylamino)-3-methylbenzonitrile

HRID 238580Notes

Reaction equation

HRID 238580 reaction equation
C([O:8][C@H:9]([C:35]([F:38])([F:37])[F:36])[C@@H:10]([NH:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([Cl:33])[C:26]=1[CH3:34])[C:11]1[O:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)=[N:14][N:15]=1)C1C=CC=CC=1.B(Br)(Br)Br>C(Cl)Cl>[Cl:33][C:27]1[C:26]([CH3:34])=[C:25]([NH:24][C@@H:10]([C:11]2[O:12][C:13]([C:16]3[CH:17]=[CH:18][C:19]([C:22]#[N:23])=[CH:20][CH:21]=3)=[N:14][N:15]=2)[C@H:9]([OH:8])[C:35]([F:36])([F:37])[F:38])[CH:32]=[CH:31][C:28]=1[C:29]#[N:30]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 666250324-((1R,2S)-2-(benzyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-3,3,3-trifluoropropylamino)-2-chloro-3-methylbenzonitrile

Product 1

HCID 498043912-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-3,3,3-trifluoro-2-hydroxypropylamino)-3-methylbenzonitrileYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-((1R,2S)-2-(benzyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-3,3,3-trifluoropropylamino)-2-chloro-3-methylbenzonitrile (170 mg, 0.32 mmol) in DCM (15 mL) was added BBr3 (380 mg, 1.52 mmol) in 0.7 mL DCM at 0° C. The reaction mixture was stirred at 0° C. for 2 h until the starting material completely disappeared. The reaction was quenched with saturated aq. NaHCO3 solution, extracted with EtOAc. The EtOAc extracts were washed with water, brine and dried over Na2SO4. After the solvent was removed, the residue was purified by flash chromatography to provide the title compound 2-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-3,3,3-trifluoro-2-hydroxypropylamino)-3-methylbenzonitrile (74.6 mg, 53%) as a white solid. 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.23 (d, J=8.6 Hz, 2H), 8.01 (d, J=8.6 Hz, 2H), 7.55 (d, J=8.6 Hz, 1H), 7.06 (d, J=8.6 Hz, 1H), 6.73 (b, 1H), 5.77 (d, J=9.4 Hz, 1H), 5.72 (dd, J=2.4, 9.0 Hz, 1H), 5.21 (m, 1H), 2.40 (s, 3H).

Workup

  1. customThe reaction was quenched with saturated aq. NaHCO3 solution
  2. extractionextracted with EtOAc
  3. washThe EtOAc extracts were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. customAfter the solvent was removed
  6. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-7ab5ff55e3e443e7869a3d038780a96b
Source dataset
uspto-grants-2014_02
Patent number
US08642632B2

Reaction notes

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