Sodium Carbonate → (1S,2R)-N-[4'-(2-Hydroxy-1-methyl-4-pyridin-3-yl-butoxy)-2-methylbiphenyl-4-yl]acetamide

HRID 380016Notes

Reaction equation

[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1.[CH3:23][C:24]1[CH:29]=[C:28]([NH:30][C:31]([CH3:33])=[O:32])[CH:27]=[CH:26][C:25]=1Br.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:25]2[CH:26]=[CH:27][C:28]([NH:30][C:31](=[O:32])[CH3:33])=[CH:29][C:24]=2[CH3:23])=[CH:7][CH:6]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Prepared according to the method described in Example 12b) from (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (0.150 g, Example 33), 4-bromo-3-methylacetanilide (0.228 g), 2M aqueous sodium carbonate (0.50 ml) and tetrakis(triphenylphosphine)palladium (0) (0.020 g) in ethanol (3 ml) with heating at 90° C. for 2 hours. After work up, the residue was purified by normal-phase HPLC eluting with a gradient of 0-25% ethanol in dichloromethane, then by reverse-phase HPLC eluting a gradient of 25-100% acetonitrile in 0.1 w/v aqueous ammonium acetate solution to give the title compound as an oil (0.041 g).

Workup

customPrepared
customAfter work up, the residue was purified by normal-phase HPLC
washeluting with a gradient of 0-25% ethanol in dichloromethane
washby reverse-phase HPLC eluting a gradient of 25-100% acetonitrile in 0.1 w/v aqueous ammonium acetate solution

Sources & evidence

ORD record: ord-5a1c6edde1f74d5cb1f4852ad4efe409
Source dataset: uspto-grants-2001_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06300352B1

Reaction notes

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