Sodium borohydride → methyl (2S)-(3-bromo-5-fluorophenyl){1-[(S)-(4-chlorophenyl)(3-cyanophenyl)methyl]azetidin-3-yl}acetate

HRID 603009Notes

Reaction equation

HRID 603009 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9](=[C:14]2[CH2:17][N:16]([C@@H:18]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]#[N:26])[CH:20]=3)[CH2:15]2)[C:10]([O:12][CH3:13])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[BH4-].[Na+]>C1COCC1.CO>[Br:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([C@@H:18]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]#[N:26])[CH:20]=3)[CH2:15]2)[C:10]([O:12][CH3:13])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 67055366Methyl (3-bromo-5-fluorophenyl){1-[(S)-(4-chlorophenyl)(3-cyanophenyl)methyl]azetidin-3-ylidene}acetate

Product 1

HCID 86612742methyl (2S)-(3-bromo-5-fluorophenyl){1-[(S)-(4-chlorophenyl)(3-cyanophenyl)methyl]azetidin-3-yl}acetate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-2.5 °C

Procedure

To a solution of 27.15 g (51.64 mmol) of methyl (3-bromo-5-fluorophenyl){1-[(S)-(4-chlorophenyl)(3-cyanophenyl)methyl]azetidin-3-ylidene}acetate in 120 mL of THF and 220 mL of MeOH, were added small portions of sodium borohydride (total: 740 mg, 31.05 mmol) at −5-0° C. The mixture stirred at −5-0° C. and the reaction was followed by HPLC. Then the reaction was quenched with 2N HCl at 0° C. (to pH=7-7.5) and concentrated to remove the organic solvents. The residue was dissolved in 300 mL of CH2Cl2 and 300 mL water, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (100 mL×2). The combined organic layer was dried over Na2SO4 and concentrated. The residue was separated by silica gel chromatography with cyclohexane/ethyl acetate to afford the methyl (2S)-(3-bromo-5-fluorophenyl){1-[(S)-(4-chlorophenyl)(3-cyanophenyl)methyl]azetidin-3-yl}acetate; 1H-NMR(CDCl3) δ 2.66(t, 1H, J=6.2 Hz), 2.92(dd, 1H, J1=7.5 Hz, J2=5.7 Hz), 3.08-3.16(m, 2H), 3.41(t, 1H, J=7.2 Hz), 3.69(s, 3H), 3.83(d, 1H, J=10.7 Hz), 4.34(s, 1H), 6.96 (d, 1H, J=8.9 Hz), 7.17(d, 1H, J=8.0 Hz), 7.20 (d, 1H, J=12 Hz), 7.27-7.32 (m, 5H), 7.39 (t, 1H, J=7.6 Hz), 7.50 (d, 1H, J=7.5 Hz), 7.60 (d, 1H, J=7.5 Hz), 7.70 (s, 1H); Mass Spectrum: m/e=527(M+1, 35Cl79Br), 529 (M+1, 37Cl79Br/35Cl81Br), 531 (M+1, 37Cl81Br).

Workup

  1. customThen the reaction was quenched with 2N HCl at 0° C. (to pH=7-7.5)
  2. concentrationconcentrated
  3. customto remove the organic solvents
  4. dissolutionThe residue was dissolved in 300 mL of CH2Cl2
  5. custom300 mL water, and the layers were separated
  6. extractionThe aqueous layer was extracted with CH2Cl2 (100 mL×2)
  7. dry with materialThe combined organic layer was dried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was separated by silica gel chromatography with cyclohexane/ethyl acetate

Sources & evidence

ORD record
ord-1f706631a7fd45909f0b6c0fe591451d
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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