Diisopropylethylamine → 6-((2'R,6'S)-3,3''-dimethyl-3',4',5',6'-terahydro-2'H-[2,2';6',2'']terpyridin-1'-yl)-hexanoic acid ethyl ester

HRID 1784208Notes

Reaction equation

HRID 1784208 reaction equation
[CH3:1][C:2]1[C:3]([C@H:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=3)[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:21]([O:23][C:24](=[O:31])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]Br)[CH3:22].CCN(C(C)C)C(C)C>CC#N>[CH2:21]([O:23][C:24](=[O:31])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][N:9]1[C@H:8]([C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH2:13][CH2:12][CH2:11][C@@H:10]1[C:14]1[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=1)[CH3:22]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 117544Ethyl 6-bromohexanoateHCID 575911373,3''-Dimethyl-1',2',3',4',5', 6'-hexahydro-cis-[2,2';6',2'']terpyridine

Product 1

HCID 674210986-((2'R,6'S)-3,3''-dimethyl-3',4',5',6'-terahydro-2'H-[2,2';6',2'']terpyridin-1'-yl)-hexanoic acid ethyl esterYield 90.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of (2′R,6′S)-3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (308 mg, 1.15 mmol), 6-bromo-hexanoic acid ethyl ester (283 mg, 1.27 mmol), DIPEA (260 μL, 1.49 mmol) and KI (10 mg, 0.060 mmol) in CH3CN (12 mL) was warmed to 60° C. and stirred for 23 h according to General Procedure A. Purification by flash chromatography on silica gel using CH2Cl2/MeOH/NH4OH (94:5:1) afforded 6-((2′R,6′S)-3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-yl)-hexanoic acid ethyl ester (425 mg, 90%) as a yellow oil. 1H NMR (CDCl3) δ 0.60-0.68 (m, 2H), 0.79-0.85 (m, 1H), 1.13-1.25 (m, 5H), 1.58-1.70 (m, 3H), 1.94-1.98 (m, 4H), 2.08-2.25 (m, 7H), 2.48 (bs, 6H), 1.50-2.63 (m, 2H), 4.03 (q, 2H, J=7.1 Hz), 7.05-7.08 (m, 2H), 7.43 (d, 2H, J=7.3 Hz), 8.47 (bs, 2H).

Workup

  1. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-53957fe214f7449597c1405a3df69165
Source dataset
uspto-grants-2009_03
Patent number
US07501518B2

Reaction notes

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