Sodium cyanoborohydride → HCID 24990821, compound

HRID 1919815Notes

Reaction equation

HRID 1919815 reaction equation
[CH3:1][C:2]([NH:14][C:15]1[C:16](=[O:40])[N:17]([C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=2)[C@@H:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH:27]3[CH2:29][CH2:28]3)[CH:21]=2)[CH:19]=1)([C:4]1[CH:5]=[N:6][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:8][CH:9]=1)[CH3:3].C([BH3-])#N.[Na+]>C(O)(=O)C>[CH3:3][C:2]([NH:14][C@@H:15]1[CH2:19][C@H:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH:27]3[CH2:29][CH2:28]3)[CH:21]=2)[N:17]([C:30]2[CH:31]=[CH:32][C:33]([C:36]([F:37])([F:39])[F:38])=[CH:34][CH:35]=2)[C:16]1=[O:40])([C:4]1[CH:5]=[N:6][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:8][CH:9]=1)[CH3:1]

Participants

4

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 86635741HCID 86635741, compound

Product 1

HCID 24990821HCID 24990821, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Add trifluoroacetic acid (1.5 mL, 20 mmol) to a mixture of (R)-3-((R)-1-phenyl-ethylamino)-5-(3-cyclopropoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-1,5-dihydro-pyrrol-2-one (1.92 g, 4.01 mmol) in toluene (10 mL) and water (4 mL). Stir at ambient temperature for 60 min. Observe significant formation of (R)-5-(3-cyclopropoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidine-2,3-dione. LCMS, Ret. time=4.14 min., Method 3, MS (m/z): 376.0 (M+), 374.0 (M−1). Add a solution of 1-methyl-1-(6-trifluoromethyl-pyridin-3-yl)-ethylamine (1.2 g, 5.9 mmol) in toluene (10 mL) to the reaction solution. Then add acetic acid (1.9 mL, 33 mmol). Heat at 50° C. for 14 hours. Concentrate under reduced pressure. Purify the residue by silica gel chromatography (0-10% ethyl acetate-hexane) to obtain (R)-3-[1-methyl-1-(6-trifluoromethyl-pyridin-3-yl)-ethylamino]-5-(3-cyclopropoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-1,5-dihydro-pyrrol-2-one as a tan foam. LCMS, Ret. time=5.40 min., Method 3, MS (m/z): 562.0 (M+), 560.0 (M−1). Dissolve (R)-3-[1-methyl-1-(6-trifluoromethyl-pyridin-3-yl)-ethylamino]-5-(3-cyclopropoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-1,5-dihydro-pyrrol-2-one (1.09 g, 1.94 mmol) in acetic acid (20 mL) and add sodium cyanoborohydride (240 mg. 3.8 mmol). Stir 1 hour at ambient temperature. Concentrate under reduced pressure. Dissolve the residue in dichloromethane and wash with saturated sodium bicarbonate solution, dry over sodium sulfate, filter and concentrate under reduced pressure. Purify the residue by silica gel chromatography (0-15% ethyl acetate-hexane) to obtain (3R,5R)-3-[1-methyl-1-(6-trifluoromethyl-pyridin-3-yl)-ethylamino]-5-(3-cyclopropoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one (645 mg, 59%) as a white foam. LCMS, Ret. time=5.04 min, Method 3 MS (m/z): 564.0 (M+1).

Workup

  1. concentrationConcentrate under reduced pressure
  2. dissolutionDissolve the residue in dichloromethane
  3. washwash with saturated sodium bicarbonate solution
  4. dry with materialdry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure
  7. customPurify the residue by silica gel chromatography (0-15% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-1f45fd94cefd4e05b458bfe8609fe740
Source dataset
uspto-grants-2012_05
Patent number
US08168659B2

Reaction notes

Loading…