4-Fluorophenylboronic acid → 2-(3,5-Dichloro-4'-fluoro-biphenyl-4-ylmethyl)-2-aza-spiro[4.5]decan-1-one

HRID 2427475Notes

Reaction equation

Br[C:2]1[CH:19]=[C:18]([Cl:20])[C:5]([CH2:6][N:7]2[CH2:11][CH2:10][C:9]3([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[C:8]2=[O:17])=[C:4]([Cl:21])[CH:3]=1.[F:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=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>[Cl:21][C:4]1[CH:3]=[C:2]([C:26]2[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=2)[CH:19]=[C:18]([Cl:20])[C:5]=1[CH2:6][N:7]1[CH2:11][CH2:10][C:9]2([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[C:8]1=[O:17]

Participants

Conditions

Temperature: 90 °C

Procedure

Purged with N2 a mixture of 2-(4-bromo-2,6-dichloro-benzyl)-2-aza-spiro[4.5]decan-1-one (0.091 g, 0.23 mmol) and 4-fluorophenylboronic acid (0.097 g, 0.69 mmol) in toluene (6 mL) and 2M sodium carbonate (0.8 mL). Treat the reaction with Pd(PPh3)4 (0.013 g, 0.011 mmol) and heat to 90° C. for 2 hours under N2. Cool the reaction and dilute with ethyl acetate, and then wash with 1N HCl and water. Dry the organic layer with Na2SO4 and remove the solvent in vacuo to afford crude product. Purify with a 0 to 100% ethyl acetate in hexanes gradient on silica gel to afford 0.096 g (100%) of the titled product. Rf=0.25 (3/1 hexanes/ethyl acetate). MS (m/z): 406 (M+).

Workup

customPurged with N2
additionTreat
temperatureCool
customthe reaction
washwash with 1N HCl and water
dry with materialDry the organic layer with Na2SO4
customremove the solvent in vacuo
customto afford crude product
customPurify with a 0 to 100% ethyl acetate in hexanes gradient on silica gel

Sources & evidence

ORD record: ord-75a9e31d71614df7a45b5ef1df4cc863
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07968585B2

Reaction notes

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