Acetic Acid → Methyl 4-((4-(((trans-2-(4-iodophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoate

HRID 534208Notes

Reaction equation

HRID 534208 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[NH2:11])=[CH:4][CH:3]=1.[CH:12]([CH:14]1[CH2:19][CH2:18][N:17]([CH2:20][C:21]2[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][CH:22]=2)[CH2:16][CH2:15]1)=O.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[I:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[CH2:10][C@H:9]2[NH:11][CH2:12][CH:14]2[CH2:19][CH2:18][N:17]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:29][CH:30]=3)[CH2:16][CH2:15]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 68385170trans-2-(4-Iodophenyl)cyclopropanamineHCID 86708256Methyl 4-((4-formylpiperidin-1-yl)methyl)benzoate

Product 1

HCID 68388443Methyl 4-((4-(((trans-2-(4-iodophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoateYield 29.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of trans-2-(4-iodophenyl)cyclopropanamine (420 mg, 1.621 mmol) in methanol (7 mL) were added methyl 4-((4-formylpiperidin-1-yl)methyl)benzoate (466 mg, 1.783 mmol), sodium cyanoborohydride (204 mg, 3.24 mmol), and acetic acid (0.028 mL, 0.486 mmol), and the mixture was stirred at room temperature for 18 h. The mixture was then quenched with saturated NaHCO3 aqueous solution (2 ml) and concentrated. The residue was treated with water (4 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated. The residue was purified using column chromatography (silica gel, 0 to 10% MeOH/EtOAc) to give 241 mg of product as pale yellow solid. MS: (M+H)+=505.3 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.97-1.16 (m, 2H), 1.19-1.38 (m, 2H), 1.46-1.63 (m, 1H), 1.71-1.92 (m, 3H), 2.00-2.10 (m, 2H), 2.29 (ddd, J=7.45, 4.42, 3.28 Hz, 1H), 2.56-2.65 (m, 2H), 2.86-2.98 (m, 2H), 3.56-3.66 (m, 2H), 3.89-3.98 (m, 3H), 6.80-6.92 (m, 2H), 7.43-7.62 (m, 4H), 7.94-8.05 (m, 2H).

Workup

  1. customThe mixture was then quenched with saturated NaHCO3 aqueous solution (2 ml)
  2. concentrationconcentrated
  3. additionThe residue was treated with water (4 mL)
  4. extractionextracted with DCM (3×)
  5. dry with materialThe extract was dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified

Sources & evidence

ORD record
ord-d260065d282b4664891ce750e5974103
Source dataset
uspto-grants-2014_10
Patent number
US08853408B2

Reaction notes

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