o-Cyclohexylphenol → HCID 57919274, compound

HRID 2381320Notes

Reaction equation

HRID 2381320 reaction equation
Cl[C:2]1[C:3](=[O:15])[N:4](C2CCCCO2)[N:5]=[CH:6][C:7]=1Cl.[CH:16]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[OH:28])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.C[O:30][C:31](=[O:40])[CH:32](Br)[CH2:33][CH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1>>[CH:16]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[O:28][C:7]2[CH:6]=[N:5][N:4]([CH:32]([CH2:33][CH:34]3[CH2:38][CH2:37][CH2:36][CH2:35]3)[C:31]([OH:30])=[O:40])[C:3](=[O:15])[CH:2]=2)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

4

Reactant 3

HCID 8396o-CyclohexylphenolHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×HCID 57919172Methyl 2-bromo-3-cyclopentylpropanoate2×

Product 1

HCID 57919274HCID 57919274, compoundYield 72%

Procedure

In an analogous manner to the stepwise sequence outlined in intermediate 19, starting from 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (Intermediate 20) and 2-cyclohexylphenol and alkylating with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10) afforded 2-[4-(2-cyclohexylphenoxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentylpropionic acid (17.1 g, 72%) as a white solid; LC-MS [M+H+]=411.2; HPLC (0.17% trifluoroacetic acid in acetonitrile/water, 50%-100% acetonitrile, gradient, 1 mL/min, Venusil MP-C18, C18-15 cm×4.6 mm-5 μm), 254 nm, 95.8%, 214 nm, 97.2%. 1H-NMR (CDCl3, 300 MHz) δ 1.04-1.77 (m, 19H), 2.05-2.11 (m, 1H), 2.22-2.31 (m, 1H), 2.59-2.66 (t, 1H), 5.27-5.32 (dd, J=10.2 Hz, 4.8 Hz, 1H), 5.88-5.89 (d, J=2.4 Hz, 1H), 6.98-7.00 (m, 1H), 7.19-7.26 (m, 2H), 7.34-7.37 (m, 1H), 7.84-7.85 (d, J=2.7 Hz, 1H).

Sources & evidence

ORD record
ord-785c7517495b4f4887a05074f6fcbbad
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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