Sodium cyanoborohydride → HCID 44247760, compound

HRID 1967567Notes

Reaction equation

HRID 1967567 reaction equation
[CH3:1][C:2]([NH:14][C:15]1[C:16](=[O:41])[N:17]([C:31]2[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=2)[C@@H:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:29])[F:28])[CH:21]=2)[CH:19]=1)([C:4]1[CH:9]=[CH:8][N:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[N:5]=1)[CH3:3].C([BH3-])#N.[Na+]>C(O)(=O)C.C1COCC1>[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][C:27]([F:28])([F:29])[F:30])[CH:21]=2)[N:17]([C:31]2[CH:32]=[CH:33][C:34]([C:37]([F:38])([F:40])[F:39])=[CH:35][CH:36]=2)[C:16]1=[O:41])([C:4]1[CH:9]=[CH:8][N:7]=[C:6]([C:10]([F:11])([F:13])[F:12])[N:5]=1)[CH3:1]

Participants

5

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 86650870HCID 86650870, compound

Product 1

HCID 44247760HCID 44247760, compoundYield 69.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

Cool a solution of (R)-3-[1-methyl-1-(2-trifluoromethyl-pyrimidin-4-yl)-ethylamino]-1-(4-trifluoromethyl-phenyl)-5-(3-trifluoromethoxy-phenyl)-1,5-dihydro-pyrrol-2-one (7.5 g, 12.7 mmol) in acetic acid (60 mL) and THF (15 mL) to 0° C. and add sodium cyanoborohydride (1.60 g, 25.4 mmol). Remove the cooling bath after 5 minutes and stir 60 minutes at ambient temperature. Dilute the reaction mixture with ethyl acetate and slowly pour into saturated aqueous sodium bicarbonate solution. Separate the organic layer and concentrate under reduced pressure. Purify the residue by silica gel chromatography (15-40% ethyl acetate-hexane) to obtain (3R,5R)-3-[1-methyl-1-(2-trifluoromethyl-pyrimidin-4-yl)-ethylamino]-5-(3-trifluoromethoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one (5.20 g, 69%) as a purple foam. To remove purple color, dissolve (3R,5R)-3-[1-methyl-1-(2-trifluoromethyl-pyrimidin-4-yl)-ethylamino]-5-(3-trifluoromethoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one in methanol (150 mL) and add activated carbon. Stir at ambient temperature for 20 min, filter, and concentrate under reduced pressure to give a white foam (4.6 g, 88%). 1H NMR (400 MHz, CDCl3): δ 8.79 (d, J=5.3 Hz, 1H), 7.90 (d, J=5.3 Hz, 1H), 7.46 (d, J=8.4 Hz, 2H), 7.36 (d, J=8.8 Hz, 2H), 7.27 (t, J=7.9 Hz, 1H), 7.08 (d, J=7.9 Hz, 1H), 7.04 (d, J=8.4 Hz, 1H), 6.98 (s, 1H), 5.04 (dd, J=6.2, 9.7 Hz, 1H), 3.51-3.45 (m, 1H), 2.90-2.81 (m, 1H), 1.89-1.81 (m, 1H), 1.56 (s, 3H), 1.50 (s, 3H). LC-MS ESI m/z: 593 (M+H)+, Tr=3.07 min., method 2.

Workup

  1. customRemove the cooling bath after 5 minutes
  2. additionDilute the reaction mixture with ethyl acetate
  3. additionslowly pour into saturated aqueous sodium bicarbonate solution
  4. customSeparate the organic layer
  5. concentrationconcentrate under reduced pressure
  6. customPurify the residue by silica gel chromatography (15-40% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-1a3b61812d70494cacc02a9ac854c499
Source dataset
uspto-grants-2013_04
Patent number
US08420654B2

Reaction notes

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