Triethylamine → HCID 86706064, compound

HRID 2176226Notes

Reaction equation

HRID 2176226 reaction equation
[C:1]([O:5][C:6](=[O:22])[N:7]([C@@H:9]([C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][C:15](Br)=[CH:16][CH:17]=2)[N:12]=1)[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[O:23]=[C:24]1[CH2:29][CH2:28][C:27]([CH:33]=[CH2:34])([C:30]([OH:32])=[O:31])[CH2:26][CH2:25]1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:7]([CH3:8])[C@@H:9]([C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][C:15](/[CH:34]=[CH:33]/[C:27]3([C:30]([OH:32])=[O:31])[CH2:28][CH2:29][C:24](=[O:23])[CH2:25][CH2:26]3)=[CH:16][CH:17]=2)[N:12]=1)[CH3:10])=[O:22])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 71303406HCID 71303406, compoundHCID 86706065HCID 86706065, compound

Product 1

HCID 86706064HCID 86706064, compoundYield 94.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-methyl-carbamic acid tert-butyl ester (200 mg, 0.55 mmol), 4-oxo-1-vinyl-cyclohexanecarboxylic acid (138 mg, 0.82 mmol), palladium(II) acetate (25 mg, 0.11 mmol), tri-(o-tolyl)phosphine (50 mg, 0.16 mmol) in anhydrous 1,4-dioxane (2 mL) was treated with triethylamine (267 μL, 1.91 mmol). After stirring at 100° C. under microwave irradiation for 30 minutes, the reaction was cooled to room temperature and the volatiles were removed in vacuo. The residue was partitioned between ethyl acetate and a 5% citric acid solution, the aqueous layer was extracted with ethyl acetate (2 x), the organics were combined and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 25 g Biotage cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 1:1 to afford the title compound (235 mg, 94%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 1.48 (s, 9H), 1.68 (d, J=7.1 Hz, 3H), 2.07-2.22 (m, 2H), 2.44-2.70 (m, 6H), 2.75 (br s, 3H), 5.61 (br s, 1H), 6.68 (ABq, ΔδAB=0.31, JAB=16.3 Hz, 2H), 7.36 (d, J=8.5 Hz, 1H), 7.60 (d, J=8.5 Hz, 1H), 7.75 (d, J=8.5 Hz, 1H), 8.05-8.12 (m, 2H). LCMS (m/z) 453.1 [M+H], Tr=2.48 min.

Workup

  1. temperaturethe reaction was cooled to room temperature
  2. customthe volatiles were removed in vacuo
  3. customThe residue was partitioned between ethyl acetate
  4. extractiona 5% citric acid solution, the aqueous layer was extracted with ethyl acetate (2 x)
  5. customthe volatiles were removed in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 1:1

Sources & evidence

ORD record
ord-ec0ccb16aff24a32b4dcddbd6a8c25bd
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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