Acetic Acid → HCID 58815898, compound

HRID 2245872Notes

Reaction equation

HRID 2245872 reaction equation
[CH2:1]([O:3][C:4](=[O:36])[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:35])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C@@H:19]([N:27]3[CH2:32][C@@H:31]([CH3:33])[NH:30][CH2:29][C@@H:28]3[CH3:34])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=3)[CH:14]=2)[CH2:8][CH2:7]1)[CH3:2].[F:37][C:38]1[CH:39]=[C:40]([CH:43]=[CH:44][CH:45]=1)[CH:41]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[CH2:1]([O:3][C:4](=[O:36])[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:35])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C@@H:19]([N:27]3[CH2:32][C@@H:31]([CH3:33])[N:30]([CH2:41][C:40]4[CH:43]=[CH:44][CH:45]=[C:38]([F:37])[CH:39]=4)[CH2:29][C@@H:28]3[CH3:34])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=3)[CH:14]=2)[CH2:8][CH2:7]1)[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 680093-FluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58815981HCID 58815981, compound

Product 1

HCID 58815898HCID 58815898, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The above free amine (1.23 g, 2.49 mmol, Example 65) and 3-fluorobenzaldehyde (0.62 g, 4.98 mmol) were placed in a 100 mL flask and sealed under nitrogen. Tetrahydrofuran (40 mL) and 0.31 mL of acetic acid (5.47 mmol, 2.20 equiv.) was added. The reaction was stirred at room temperature for 20 minutes, and then sodium triacetoxyborohydride (1.32 g, 6.22 mmol) was added and stirred overnight. The reaction solution was concentrated under reduced pressure. The residue was partitioned between ethyl acetate (50 mL) and saturated sodium hydrogencarbonate (25 mL). The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residual dark brown oil (2.01 g) was purified by chromatography on a Biotage column (SiO2-F Flash Cartridge, 8 g, 32-63 μm, 60 A) eluting first with dichloromethane to remove the less polar contaminant, then using 2.5% methanol in dichloromethane. The desired fractions were combined and the solvent was removed under reduced pressure. The title product (4-{3-[(R)-[(2S,5R)-4-(3-fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperazin-1-yl)-acetic acid ethyl ester was obtained as a light yellow solid (0.75 g, 50%). 1H NMR (300 MHz, d6-DMSO): □ 0.81-1.01 (m, 6H); 1.14-1.19 (t, 3H), 1.89-2.01 (m, 2H); 2.48 (s, 4H); 2.57-2.66 (m, 4H); 3.24 (s, 2H); 3.29-3.36 (m, 4H); 3.50-3.56 (m, 1H); 3.71-3.76 (dd, 1H); 4.03-4.10 (q, 2H); 4.94 (s, 1H); 6.62-6.71 (m, 3H); 6.97-7.19 (m, 4H); 7.29-7.43 (m, 5H); 9.35 (s, 1H). Calculated for C35H43FN4O4.0.12 CH2Cl2: C, 68.82; H, 7.11; N, 9.14; F, 3.10. Found: C, 68.85; H, 7.17; N, 9.11; F, 3.18.

Workup

  1. customsealed under nitrogen
  2. stirringstirred overnight
  3. concentrationThe reaction solution was concentrated under reduced pressure
  4. customThe residue was partitioned between ethyl acetate (50 mL) and saturated sodium hydrogencarbonate (25 mL)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residual dark brown oil (2.01 g) was purified by chromatography on a Biotage column (SiO2-F Flash Cartridge, 8 g, 32-63 μm, 60 A)
  9. washeluting first with dichloromethane
  10. customto remove the less polar contaminant
  11. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-31a2a2cb769b4fcca8c1ba4c214d70ba
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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