Cesium carbonate → 6-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenyl}-nicotinic acid methyl ester

HRID 1095905Notes

Reaction equation

B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:25]1[CH:30]=[CH:29][C:28]([CH:31]([CH3:45])[C:32]([C:38]2[CH:43]=[CH:42][N:41]=[C:40]([CH3:44])[CH:39]=2)([OH:37])[C:33]([F:36])([F:35])[F:34])=[C:27]([Cl:46])[CH:26]=1.[CH3:47][O:48][C:49](=[O:57])[C:50]1[CH:55]=[CH:54][C:53](Cl)=[N:52][CH:51]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O>[CH3:47][O:48][C:49](=[O:57])[C:50]1[CH:55]=[CH:54][C:53]([C:25]2[CH:30]=[CH:29][C:28]([CH:31]([CH3:45])[C:32]([OH:37])([C:38]3[CH:43]=[CH:42][N:41]=[C:40]([CH3:44])[CH:39]=3)[C:33]([F:36])([F:35])[F:34])=[C:27]([Cl:46])[CH:26]=2)=[N:52][CH:51]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of bis(pinacolato)diboron (28 mg), potassium acetate (29 mg), bis(triphenylphosphine)palladium(II)chloride (2 mg), and 3-(4-bromo-2-chloro-phenyl)-1,1,1-trifluoro-2-(2-methyl-pyridin-4-yl)-butan-2-ol (Example 60 step 1, 41 mg) in dioxane (2 ml) was heated at 100° C. for 1.5 h. After cooling to room temperature, water (0.2 ml), methyl-6-chloronicotinate (CAS Reg. No. 73781-91-6, 34 mg), dichloro[1,1′-bis(diphenylphosphino)-ferrocene]palldadium(II) dichloromethane complex (11 mg) and Cs2CO3 (98 mg) were added. The mixture was heated to 100° C. for 3 h and then purified by prep. HPLC (C18-column, solvent gradient 20-98% CH3CN in 0.1% HCOOH[aq]) to give the title compound (22 mg) as a yellow solid. MS (m/e)=465.1 [M+H+].

Workup

temperatureAfter cooling to room temperature
temperatureThe mixture was heated to 100° C. for 3 h
custompurified by prep

Sources & evidence

ORD record: ord-3a6fcbb506e84ab489ac8d01c593e61a
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08138189B2

Reaction notes

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