Diisopropyl Ether → N-[(9R)-6,7,8,9-Tetrahydro-5H-cyclohepta[b]pyridin-9-yl]acetamide

HRID 271819Notes

Reaction equation

HRID 271819 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]2[CH2:7][CH2:8][CH2:9][CH2:10][CH:11]([NH2:12])[C:2]=12.[CH3:13][CH2:14][O:15]C(C)=O.O(C(C)C)C(C)C.[NH4+].[OH-]>C(Cl)Cl.CO>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]2[CH2:7][CH2:8][CH2:9][CH2:10][C@@H:11]([NH:12][C:14](=[O:15])[CH3:13])[C:2]=12

Participants

7

Reactant 4

HCID 7914Diisopropyl EtherHCID 8857Ethyl AcetateHCID 14923Ammonium HydroxideHCID 12099066HCID 12099066, compound

Product 1

HCID 12100410N-[(9R)-6,7,8,9-Tetrahydro-5H-cyclohepta[b]pyridin-9-yl]acetamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

Following the general procedure, 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ylamine (195 mg, 1.20 mmol), CALB (59 mg), EtOAc (0.48 mL) and iPr2O (4.6 mL) were stirred for 24 hours. The conversion determined from 1H NMR by integration of the peaks at 5.05 ppm (CHNHAc) and 4.34 ppm (CHNH2) was 58%. Flash chromatography of the material on silica gel using 1:10 MeOH:CH2Cl2 followed by 1:1:4 NH4OH:MeOH:CH2Cl2 furnished the (R)-N-(6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl)acetamide ((134 mg, 55%) in 45% ee (chiral GC method: 180° C. for 15 min, ramp rate of 10° C./min to 210° C., hold 10 min, (S)-(−)-enantiomerrt=17.4 min, (R)-(+)-enantiomerrt=17.1 min); [α]D=−10° (c 1.34, CHCl3); 1H NMR (CDCl3, 300 MHz) δ1.09-1.31 (m, 2H), 1.80-2.03 (m, 3H), 2.06 (s, 3H), 2.24 (d, 1H, J=13.5 Hz), 2.65-2.71 (m, 1H), 2.75-2.85 (m, 1H), 4.96-5.01 (m, 1H), 7.06 (dd, 1H, J=7.0, 4.8 Hz), 7.38 (d, 1H, J=7.0 Hz), 8.11 (br s, 1H), 8.28 (d, 1H, J=4.8 Hz); 13C NMR (CDCl3) δ 24.0, 27.3, 30.1, 34.5, 34.8, 53.8, 122.8, 137.0, 137.5, 145.5, 159.2, 169.6; MS m/z: 205 (M+H+). The unreacted (S)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ylamine (was isolated in 41% yield (81 mg) and 61% ee (chiral GC, (S)-enantiomerrt=5.81 min, (R)-enantiomerrt=6.00 min); [α]D=+2° (c 1.13, CHCl3); and displayed spectra identical to the starting material: 1H NMR (CDCl3, 300 MHz) δ 1.20-1.35 (m, 1H), 1.36-1.53 (m, 1H), 1.75-2.01 (m, 4H), 2.15 (br s, 2H), 2.69-2.77 (m, 2H), 4.16 (d, 1H, J=8.7 Hz), 6.95-7.06 (m, 1H), 7.32 (d, 1H, J=6.0 Hz), 8.34 (br s, 1H).

Sources & evidence

ORD record
ord-c70d6d935e8b4acf86611ea9e8792174
Source dataset
uspto-grants-2008_11
Patent number
US07452994B2

Reaction notes

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