Acetic Acid → 1-{3-[(R)-1-(4-Chloro-3-methyl-phenyl)-propylamino]-benzyl}-3-methyl-azetidine-3-carboxylic acid methyl ester

HRID 1629711Notes

Reaction equation

HRID 1629711 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:11][C:12]2[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=2)[CH:15]=O)[CH2:9][CH3:10])=[CH:4][C:3]=1[CH3:20].Cl.[CH3:22][O:23][C:24]([C:26]1([CH3:30])[CH2:29][NH:28][CH2:27]1)=[O:25].CCN(C(C)C)C(C)C.CC(O)=O.[BH3-]C#N.[Na+]>CO>[CH3:22][O:23][C:24]([C:26]1([CH3:30])[CH2:29][N:28]([CH2:15][C:14]2[CH:17]=[CH:18][CH:19]=[C:12]([NH:11][C@@H:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([CH3:20])[CH:4]=3)[CH2:9][CH3:10])[CH:13]=2)[CH2:27]1)=[O:25]

Participants

7

Reactant 5

HCID 176Acetic Acid2×HCID 81531Diisopropylethylamine2×HCID 5003444Sodium cyanoborohydrideHCID 575173193-[(R)-1-(4-Chloro-3-methyl-phenyl)-propylamino]-benzaldehydeHCID 67329141Methyl 3-methylazetidine-3-carboxylate hydrochloride2×

Product 1

HCID 673297101-{3-[(R)-1-(4-Chloro-3-methyl-phenyl)-propylamino]-benzyl}-3-methyl-azetidine-3-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a mixture of INT 7 (250 mg, 0.87 mmol) and INT 14 (158 mg, 0.88 mmol) in MeOH (8.6 mL) was added DIPEA (0.18 mL, 1.04 mmol). Then HOAc (0.099 mL, 1.74 mmol) was added followed by NaCNBH3 (55 mg, 0.87 mmol). The reaction mixture was stirred at room temperature for 4 hours. A solution of INT 14 (50 mg, 0.091 mmol), DIPEA (0.060 mL, 0.021 mmol) and HOAc (0.040 mL, 0.70 mmol) in MeOH (1.0 mL) was added. The mixture was stirred at room temperature for another hour. The mixture was concentrated. The residue was taken up in CH2Cl2 and washed with saturated aqueous NaHCO3 and brine. The organic layer was dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel (heptane/EtOAc) to give INT 15.

Workup

  1. stirringThe mixture was stirred at room temperature for another hour
  2. concentrationThe mixture was concentrated
  3. washwashed with saturated aqueous NaHCO3 and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel (heptane/EtOAc)
  8. customto give INT 15

Sources & evidence

ORD record
ord-e27c56e1a3c742edb76ccba74206deef
Source dataset
uspto-grants-2014_07
Patent number
US08791100B2

Reaction notes

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