Sodium Carbonate → Methyl 6-amino-2-(3-(tert-butoxycarbonyl)phenyl)nicotinate

HRID 1442793Notes

Reaction equation

[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4](Cl)[N:3]=1.[C:13]([O:17][C:18]([C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])[CH:21]=2)[N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a flask containing methyl 6-amino-2-chloronicotinate (300 mg, 1.6 mmol), 3-(tert-butoxycarbonyl)phenylboronic acid (540 mg, 2.4 mmol) and Pd(PPh3)4 (90 mg, 0.080 mmol) was added DME (16 mL) and saturated Na2CO3 aqueous solution (1.6 mL). The flask was flushed with N2 (g) and heated at 80° C. under N2 atmosphere overnight. The solution was filtered and concentrated. The residue was purified by column chromatography (0-50% ethyl acetate—hexanes) to yield methyl 6-amino-2-(3-(tert-butoxycarbonyl)phenyl)nicotinate as a white solid (450 mg, 85%). ESI-MS m/z calc. 328.1, found 329.3 (M+1)+. Retention time 1.19 minutes. 1H NMR (400 MHz, DMSO-d6) δ 7.91-7.86 (m, 3H), 7.59-7.57 (m, 1H), 7.49 (t, J=7.6 Hz, 1H), 6.86 (s, 2H), 6.48 (d, J=8.7 Hz, 1H), 3.54 (s, 3H), 1.56 (s, 9 H).

Workup

customThe flask was flushed with N2 (g)
filtrationThe solution was filtered
concentrationconcentrated
customThe residue was purified by column chromatography (0-50% ethyl acetate—hexanes)

Sources & evidence

ORD record: ord-cf5e1223335246a7901f74140eda9b16
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07659268B2

Reaction notes

Loading…