Sodium Bicarbonate → Tert-butyl 4-{[3-(methoxycarbonyl)-2-methyl-5-(trifluoromethyl)phenyl]amino}piperidine-1-carboxylate

HRID 2208663Notes

Reaction equation

[NH2:1][C:2]1[C:3]([CH3:16])=[C:4]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:17]([N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C:25]1=O)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.CC(O)=O>[C:20]([O:19][C:17]([N:24]1[CH2:29][CH2:28][CH:27]([NH:1][C:2]2[CH:11]=[C:10]([C:12]([F:13])([F:14])[F:15])[CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]=2[CH3:16])[CH2:26][CH2:25]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]

Participants

Conditions

Temperature: 23 °C

Procedure

To a stirred solution of methyl 3-amino-2-methyl-5-(trifluoromethyl)benzoate (6.00 g, 25.7 mmol) in CH2Cl2 (120 mL) and AcOH (6 mL) was added N-Boc piperidinone (6.70 g, 33.4 mmol) and sodium triacetoxyborohydride (13.6 g, 64.3 mmol). The reaction mixture was stirred at 23° C. for 20 hours. Then saturated NaHCO3 was added and the mixture was separated. The aqueous layer was extracted with CH2Cl2 (3×50 mL) and the combined organic layer were concentrated in vacuo. The residue was purified by silica gel column chromatography (SiO2 heptane/EtOAc=4/1) to give the titled compound (10.6 g, 98% yield). 1H-NMR (400 MHz, CDCl3) δppm; 7.37 (s, 1H), 6.88 (s, 1H), 4.05 (m, 2H), 3.90 (s, 3H), 3.01 (m, 3H), 2.32 (s, 3H), 1.71 (m, 2H), 1.48-1.61 (m, 2H), 1.45 (s, 9H); MS (ES) [M−H] 415.1.

Workup

customthe mixture was separated
extractionThe aqueous layer was extracted with CH2Cl2 (3×50 mL)
concentrationthe combined organic layer were concentrated in vacuo
customThe residue was purified by silica gel column chromatography (SiO2 heptane/EtOAc=4/1)

Sources & evidence

ORD record: ord-fdf4a6e2f8c44b75a3120b82cd162a45
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376422B2

Reaction notes

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