Ethyl Acetate → Methyl 6-(7-benzyl-2,7-diazaspiro[4.4]non-2-yl)nicotinate

HRID 2360552Notes

Reaction equation

[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]2([CH2:16][CH2:15][NH:14][CH2:13]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][N:19]=1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CS(C)=O>[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]2([CH2:13][N:14]([C:18]3[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][N:19]=3)[CH2:15][CH2:16]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 2-benzyl-2,7-diazaspiro[4.4]nonane (1.00 g, 4.68 mmol), methyl 6-chloronicotinate (800 mg, 4.68 mmol) and K2CO3 (700 mg, 5.07 momol) in 5 mL of DMSO was stirred under microwave irradiation for 20 min at a temperature of 150° C. The mixture was poured into EtOAc and washed with sat'd NaHCO3, dried (Na2SO4), filtered and concentrated, giving methyl 6-(7-benzyl-2,7-diazaspiro[4.4]non-2-yl)nicotinate. A bottle containing a suspension of the benzyl amine and 20% Pd(OH)2/C (600 mg, 0.857 mmol) in 20 mL of EtOH was evacuated and purged with H2 gas three times. Using a Parr shaker apparatus, the suspension was agitated under 50 psi of H2 for 20 h. The pressure was released and the mixture filtered through a pad of Celite and concentrated, giving methyl 6-(2,7-diazaspiro[4.4]non-2-yl)nicotinate: 1H NMR (600 MHz, DMSO-d6) δ 8.59 (d, J=2.1 Hz, 1 H), 7.89 (dd, J=9.1, 2.3 Hz, 1 H), 7.27 (d, J=4.4 Hz, 1 H), 6.44 (d, J=8.8 Hz, 1 H), 3.74 (s, 3 H), 3.13 (br s, 4 H), 2.89 (t, J=7.3 Hz, 2 H), 2.72 (AB, J=7.6 Hz, 2 H), 1.92 (br m, 2 H), 1.69 (AB, J=7.3 Hz, 2 H).

Workup

washwashed with sat'd NaHCO3
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-14eabe897fec4f028b9bf406788bf0de
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08686020B2

Reaction notes

Loading…