Sodium hydride → 5'-bromo-5,6,8,9-tetrahydro-3'H-spiro[benzo[7]annulene-7,2'-benzofuran]-3'-one

HRID 1503384Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([C:8]([C:10]2([OH:21])[CH2:16][CH2:15][C:14]3[CH:17]=[CH:18][CH:19]=[CH:20][C:13]=3[CH2:12][CH2:11]2)=[O:9])[CH:7]=1.[H-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:21][C:10]3([CH2:16][CH2:15][C:14]4[CH:17]=[CH:18][CH:19]=[CH:20][C:13]=4[CH2:12][CH2:11]3)[C:8](=[O:9])[C:6]=2[CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (5-bromo-2-fluorophenyl)(7-hydroxy-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)methanone (1.3739 g, 3.78 mmol) and 60% NaH (0.5900 g, 14.75 mmol) in THF (20 mL) was heated at 100° C. for 1 h. The reaction mixture was then cooled with an ice bath and quenched with 2 N HCl (5 mL), extracted with ethyl acetate, dried over Na2SO4. After the solvents were evaporated, the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate to afford 0.9170 g (71%) of 5′-bromo-5,6,8,9-tetrahydro-3′H-spiro[benzo[7]annulene-7,2′-benzofuran]-3′-one as a solid. LC-MS tR=2.31 min in 3 min chromatography, m/z 343, 345 (MH+); 1H NMR (400 MHz, CDCl3) δ 7.79-7.78 (m, 1H), 7.73-7.71 (m, 1H), 7.17 (m, 4H), 7.11-7.09 (m, 1H), 3.41-3.35 (m, 2H), 2.78-2.75 (m, 2H), 1.95-1.85 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 201.53, 169.46, 141.50, 140.56, 128.93, 127.47, 126.62, 121.63, 115.61, 114.15, 92.58, 32.98, 29.67.

Workup

temperatureThe reaction mixture was then cooled with an ice bath
customquenched with 2 N HCl (5 mL)
extractionextracted with ethyl acetate
dry with materialdried over Na2SO4
customAfter the solvents were evaporated
customthe residue was purified by chromatography on silica gel
washeluted with hexanes/ethyl acetate

Sources & evidence

ORD record: ord-77a27a3ee5d24bcea20f2bbada9bbfd3
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212153B2

Reaction notes

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