Water → Ethyl acetate methanol ammonium hydroxide

(A mixture of two diastereomers.) To (+/−)-6-Methoxy-1,3-dimethyl-2-oxo-2,3-dihydro-1H-indole-5-carbaldehyde (220 mg, 1.0 mmol) and (2S,3S)-2-phenyl-piperidin-3-ylamine dihydrochloride (249 mg, 1.0 mmol) in toluene (20 mL) and methanol (2 mL) was added triethylamine (222 mg, 2.2 mmol). The solution was heated to reflux with azeotropic water removeal for 72 hours. The resultant mixture was concentrated, and the residue was suspended in 10 mL of CH2Cl2. Sodium triacetoxyborohydride (1.8 mmol, 1.8 mL of a 1 M solution in CH2Cl2) was added and the mixture was stirred at room temperature for 30 minutes. The mixture was then quenched with saturated NaHCO3 and extracted twice with CH2Cl2. The combined organic material was washed with brine, dried over NaHCO3 and concentrated. Silica gel chromatography (90:9:1 EtOAc/MeOH/NH4OH) gave 109 mg (29%) of a 1:1 mixture of title compounds as a pale yellow oil. The solid dihydrochloride salt was generated by treatment with excess HCl in ether followed by concentration in vacuo.

1. addition(A mixture of two diastereomers
2. temperatureThe solution was heated
3. concentrationThe resultant mixture was concentrated
4. additionSodium triacetoxyborohydride (1.8 mmol, 1.8 mL of a 1 M solution in CH2Cl2) was added
5. customThe mixture was then quenched with saturated NaHCO3
6. extractionextracted twice with CH2Cl2
7. washThe combined organic material was washed with brine
8. dry with materialdried over NaHCO3
9. concentrationconcentrated

ORD record

ord-cd3ac6ff716c45c9925ececb22fe4f4c

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07119207B2