Acetic Acid → tert-Butyl 4-((((trans)-2-(4-iodophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxylate

HRID 529358Notes

Reaction equation

HRID 529358 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]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=O.C(O)(=O)C.C([BH3-])#N.[Na+]>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]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:16][CH2:15]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 68385170trans-2-(4-Iodophenyl)cyclopropanamine

Product 1

HCID 86708257tert-Butyl 4-((((trans)-2-(4-iodophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxylateYield 46.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of trans-2-(4-iodophenyl)cyclopropanamine (1.0 g, 3.86 mmol) in methanol (15 mL) were added tert-butyl 4-formylpiperidine-1-carboxylate (0.741 g, 3.47 mmol), acetic acid (0.066 mL, 1.158 mmol), and the mixture was stirred at rt for 1 h. Sodium cyanoborohydride (0.364 g, 5.79 mmol) was added and the mixture was stirred at room temperature for 18 h. The mixture was concentrated and the residue was treated with water (2 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated. The residue was purified using column chromatography (silica gel, 0 to 100% EtOAc/hexanes) to give 730 mg of product as pale yellow oil. MS: (M+H)+=457.2. 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.99-1.18 (m, 3H), 1.45-1.51 (m, 9H), 1.69-1.81 (m, 3H), 1.87-1.94 (m, 1H), 2.29-2.37 (m, 1H), 2.62-2.90 (m, 3H), 4.00-4.20 (m, 2H), 6.86-6.88 (m, 2H), 7.57-7.59 (m, 2H).

Workup

  1. stirringthe mixture was stirred at room temperature for 18 h
  2. concentrationThe mixture was concentrated
  3. additionthe residue was treated with water (2 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-978be00030a742baa641381b4bd97804
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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