Methanol → N-[(5R)-5,6,7,8-Tetrahydro-5-quinolinyl]acetamide

HRID 271813Notes

Reaction equation

HRID 271813 reaction equation
[N:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH:6]([NH2:11])[C:5]=2[CH:4]=[CH:3][CH:2]=1.C[CH2:13][O:14][C:15]([CH3:17])=[O:16].[O:18](C(C)C)C(C)C.CO.[CH2:27]([Cl:29])[Cl:28]>>[CH2:27]([Cl:29])[Cl:28].[CH3:13][OH:14].[NH4+:1].[OH-:18].[N:1]1[C:10]2[CH2:9][CH2:8][CH2:7][C@@H:6]([NH:11][C:15](=[O:16])[CH3:17])[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 6344DichloromethaneHCID 7914Diisopropyl EtherHCID 8857Ethyl AcetateHCID 1561825,6,7,8-Tetrahydroquinolin-5-amine

Product 2

HCID 12100404N-[(5R)-5,6,7,8-Tetrahydro-5-quinolinyl]acetamideHCID 21896990Dichloromethane methanol ammonium hydroxide

Procedure

Following the general procedure, 5,6,7,8-tetrahydroquinolin-5-ylamine (213.2 mg, 1.44 mmol), CALB (64 mg), EtOAc (0.56 mL) and iPr2O (4.8 mL) were stirred for 6 hours. The conversion determined from 1H NMR by integration of the peaks at 5.07 ppm (CHNHAc) and 3.91 ppm (CHNH2) was 50%. Flash chromatography of the material on silica gel using 1:10 MeOH:CH2Cl2 then 20:2:1 CH2Cl2-MeOH-NH4OH furnished (R)-N-(5,6,7,8-tetrahydroquinolin-5-yl)acetamide ((132 mg, 48%) in 98% ee (chiral GC method: isothermal at 85° C. for 220 minutes ramp 5° C./min to 210° C., hold 5 min, (S)-enantiomerrt=248.2 min, (R)-enantiomerrt=248.5 min); [α]D=+110° (c 1.32, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 1.69-1.81 (m, 1H), 1.84-2.00 (m, 2H), 2.04 (s, 3H), 2.01-2.18 (m, 1H), 2.86-2.99 (m, 2H), 5.19-5.27 (m, 1H), 5.78 (br s, 1H), 7.10 (dd, 1H, J=7.8, 4.8 Hz), 7.58 (d, 1H, J=7.8 Hz), 8.41 (d, 1H, J=4.8 Hz); 13C NMR (CDCl3) δ 20.2, 23.8, 30.1, 32.6, 47.4, 121.9, 133.0, 136.9, 148.7, 157.7, 170.0; MS m/z: 191 (M+H+). The unreacted (S)-5,6,7,8-tetrahydroquinolin-5-ylamine (was isolated in 48% yield (103 mg) and 99% ee (chiral GC: (S)-enantiomerrt=236.0 min, (R)-enantiomerrt=236.6 min); [α]D=+39° (c 1.03, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 1.50-1.70 (m, 3H), 1.74-1.85 (m 1H), 1.86-2.09 (m, 2H), 2.76-2.99 (m, 2H), 3.94 (m, 1H), 7.07 (dd, 1H, J=7.8, 4.5 Hz), 7.70 (d, 1H, J=7.8 Hz), 8.35 (dd, 1H, J=4.5, 1.5 Hz); 13C NMR (CDCl3) δ 19.8, 32.9, 34.0, 49.6, 121.7, 136.2, 136.6, 148.1, 157.3; MS m/z: 149 (M+H+).

Sources & evidence

ORD record
ord-ce62bcf6c5ae40fea4d50df39b987f23
Source dataset
uspto-grants-2008_11
Patent number
US07452994B2

Reaction notes

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