Potassium Carbonate → 1,1-Dimethylethyl 4-{[3-(4-cyano-2-pyridinyl)phenyl]methyl}-1-piperidinecarboxylate

HRID 662093Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=1.[CH3:10][C:11]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][C:24]2[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])[CH3:12].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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>[C:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:26]2[CH:25]=[C:24]([CH2:23][CH:20]3[CH2:19][CH2:18][N:17]([C:15]([O:14][C:11]([CH3:13])([CH3:12])[CH3:10])=[O:16])[CH2:22][CH2:21]3)[CH:29]=[CH:28][CH:27]=2)[CH:7]=1)#[N:9]

Participants

Conditions

Temperature: 140 °C

Procedure

To 2-chloro-4-pyridinecarbonitrile (416 mg, 3 mmol) was added {3-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)methyl]phenyl}boronic acid (958 mg, 3.00 mmol) followed by K2CO3 (1,244 mg, 9.00 mmol) and Pd(Ph3P)4 (139 mg, 0.120 mmol) in 1,4-dioxane (15 mL) and water (5 mL). The mixture was heated in a microwave for 30 min at 140° C. The organic layer was collected and the aqueous layer was extracted with EtOAc (3 mL). The combined organic layers were filtered, evaporated on Glas-Col, redissolved in hexane/DCM 4 mL (3/1), loaded onto Redisep gel column (40 g) and purified with the Combiflash chromatograph to afford 640 mg (57%) of the title compound. LC-MS m/z 378 (M+H)+.

Workup

customThe organic layer was collected
extractionthe aqueous layer was extracted with EtOAc (3 mL)
filtrationThe combined organic layers were filtered
customevaporated on Glas-Col
dissolutionredissolved in hexane/DCM 4 mL (3/1)
custompurified with the Combiflash chromatograph

Sources & evidence

ORD record: ord-78804a9310c44bbd93806c4684416cde
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08084449B2

Reaction notes

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