Isobutyraldehyde → (R)-Methyl 3-(isobutylamino)-2,3-dihydro-1H-indene-5-carboxylate

HRID 1193252Notes

Reaction equation

[NH2:1][C@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=2)[CH2:4][CH2:3]1.[CH:15](=O)[CH:16]([CH3:18])[CH3:17].[BH3-]C#N.[Na+]>CO.C(O)(=O)C>[CH2:15]([NH:1][C@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=2)[CH2:4][CH2:3]1)[CH:16]([CH3:18])[CH3:17]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (R)-methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate (A-07) (5.23 mmol, 1 eq) in MeOH (50 ml) there were added first acetic acid (2 drops) and then, at 0° C., isobutyraldehyde (0.47 ml, 5.23 mmol, 1 eq), and stirring was carried out for 1 h at RT. The reaction mixture was cooled to 0° C. again, NaCNBH3 (821 mg, 13.07 mmol, 2.5 eq) was added, and stirring was carried out for a further 30 min at RT. After monitoring by thin-layer chromatography, the reaction mixture was concentrated, and the residue was taken up in water (50 ml) and extracted with dichloromethane (2×75 ml). The combined organic phases were washed with sat. NaCl solution (2×60 ml), dried over sodium sulfate and concentrated under reduced pressure. After purification by column chromatography (Alox neutral, 3% MeOH in dichloromethane), the desired product was obtained. Yield: 65% (0.850 g, 33.44 mmol).

Workup

waitwas carried out for a further 30 min at RT
concentrationthe reaction mixture was concentrated
extractionextracted with dichloromethane (2×75 ml)
washThe combined organic phases were washed with sat. NaCl solution (2×60 ml)
dry with materialdried over sodium sulfate
concentrationconcentrated under reduced pressure
customAfter purification by column chromatography (Alox neutral, 3% MeOH in dichloromethane)

Sources & evidence

ORD record: ord-c4a99905ca7347cea4a23dc84cf0321b
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680159B2

Reaction notes

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