3-(Trifluoromethyl)benzaldehyde → 3,3-bis(4-fluorophenyl)-1-(2-oxo-2-{(4aS,7aS)-1-[3-(trifluoromethyl)benzyl]octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl}ethyl)pyrrolidin-2-one

HRID 1667247Notes

Reaction equation

HRID 1667247 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[CH2:12][CH2:11][N:10]([CH2:13][C:14](=[O:24])[N:15]3[CH2:23][C@H:22]4[C@H:17]([NH:18][CH2:19][CH2:20][CH2:21]4)[CH2:16]3)[C:9]2=[O:25])=[CH:4][CH:3]=1.[F:33][C:34]([F:44])([F:43])[C:35]1[CH:36]=[C:37]([CH:40]=[CH:41][CH:42]=1)[CH:38]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(O)(=O)C.ClCCl>[F:32][C:29]1[CH:28]=[CH:27][C:26]([C:8]2([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[CH2:12][CH2:11][N:10]([CH2:13][C:14](=[O:24])[N:15]3[CH2:23][C@H:22]4[C@H:17]([N:18]([CH2:38][C:37]5[CH:40]=[CH:41][CH:42]=[C:35]([C:34]([F:33])([F:43])[F:44])[CH:36]=5)[CH2:19][CH2:20][CH2:21]4)[CH2:16]3)[C:9]2=[O:25])=[CH:31][CH:30]=1

Participants

7

Reactant 3

HCID 679903-(Trifluoromethyl)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 674471943,3-bis(4-fluorophenyl)-1-(2-oxo-2-((4aS,7aS)-tetrahydro-1H-pyrrolo[3,4-b]pyridin-6(2H,7H,7aH)-yl)ethyl)pyrrolidin-2-one

Product 1

HCID 452746103,3-bis(4-fluorophenyl)-1-(2-oxo-2-{(4aS,7aS)-1-[3-(trifluoromethyl)benzyl]octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl}ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of product from Example 210A (0.2 g, 0.455 mmol) in dichloroethane (10 mL) was added 3-(trifluoromethyl)benzaldehyde (0.135 g, 0.774 mmol), sodium triacetoxyborohydride (0.145 g, 0.683 mmol), and a few drops of acetic acid. The reaction mixture was stirred at room temperature for 16 hours, then diluted with dichloromethane and washed with saturated aqueous NaHCO3 solution. The organic layer was separated, dried over MgSO4, concentrated and purified by silica gel chromatography eluting with 2-5% methanol/dichloromethane. 1H NMR (400 MHz, pyridine-d5, temperature 90° C.) δ ppm 7.63-7.72 (m, 1H), 7.55-7.63 (m, 4H), 7.47-7.58 (m, 2H), 7.33-7.45 (m, 1H), 7.00-7.08 (m, 4H), 4.13-4.33 (m, 2H), 3.66-3.77 (m, 1H), 3.51-3.65 (m, 3H), 3.27-3.65 (m, 4H), 2.87-3.15 (m, 1H), 2.73-2.80 (m, 2H), 2.45-2.57 (m, 1H), 2.06-2.26 (m, 2H), 1.23-1.56 (m, 4H); MS (ESI+) m/z 599 (M+H)+.

Workup

  1. washwashed with saturated aqueous NaHCO3 solution
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. custompurified by silica gel chromatography
  6. washeluting with 2-5% methanol/dichloromethane

Sources & evidence

ORD record
ord-840e837e25b7452191c4a466f7e84277
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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