Acetic Acid → (R)-methyl 4-(1-((1-methylcyclohexyl)methylamino)ethyl)benzoate

HRID 1049100Notes

Reaction equation

HRID 1049100 reaction equation
[NH2:1][C@@H:2]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)[CH3:3].CO.[CH3:16][C:17]1([CH:23]=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C(O)(=O)C.C([BH3-])#N.[Na+]>>[CH3:16][C:17]1([CH2:23][NH:1][C@@H:2]([C:4]2[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=2)[CH3:3])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 111371681-Methylcyclohexane-1-carboxaldehydeHCID 17751897(R)-Methyl 4-(1-aminoethyl)benzoate

Product 1

HCID 67395199(R)-methyl 4-(1-((1-methylcyclohexyl)methylamino)ethyl)benzoateYield 63.4%

Procedure

To a solution of (R)-methyl 4-(1-aminoethyl)benzoate (0.12 g, 0.67 mmol) in methanol (2.97 mL, 73.33 mmol) was added 1-methylcyclohexane-1-carboxaldehyde (0.093 g, 0.74 mmol) and acetic acid (0.152 mL, 2.67 mmol). The reaction was stirred for 1 hour at room temperature whereupon sodium cyanoborohydride (63.1 mg, 1.00 mmol) was added and the mixture further stirred at room temperature overnight. The solvent was evaporated and the residual sodium cyanoborohydride quenched with saturated aqueous NaHCO3. The mixture was extracted into ethyl acetate, the organic layer washed with brine and the solvent evaporated to dryness. The residue obtained was purified via silica chromatography (0-5% MeOH/DCM) to afford the title compound as a colorless oil (123.0 mg, 63%). LC-MS: (FA) ES+ 290.

Workup

  1. additionwas added
  2. customThe solvent was evaporated
  3. customthe residual sodium cyanoborohydride quenched with saturated aqueous NaHCO3
  4. extractionThe mixture was extracted into ethyl acetate
  5. washthe organic layer washed with brine
  6. customthe solvent evaporated to dryness
  7. customThe residue obtained
  8. customwas purified via silica chromatography (0-5% MeOH/DCM)

Sources & evidence

ORD record
ord-ef45cbb639e541f79c24a6a042314063
Source dataset
uspto-grants-2016_07
Patent number
US09382197B2

Reaction notes

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