1,4-Dioxane → HCID 178517856, compound

HRID 1044345Notes

Reaction equation

HRID 1044345 reaction equation
Cl.[OH:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([N:9]2[CH2:13][CH2:12][C:11]3([CH2:18][CH2:17][CH2:16][NH:15][CH2:14]3)[C:10]2=[O:19])[CH2:5][CH2:4]1.Br[C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.O1CCOCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([N:9]2[CH2:13][CH2:12][C:11]3([CH2:18][CH2:17][CH2:16][N:15]([C:21]4[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=4)[CH2:14]3)[C:10]2=[O:19])[CH2:5][CH2:4]1

Participants

7

Reactant 5

HCID 312751,4-DioxaneHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 178479652HCID 178479652, compound

Product 1

HCID 178517856HCID 178517856, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(trans-4-hydroxycyclohexyl)-2,7-diazaspiro[4.5]decan-1-one hydrochloride (25 mg, 0.000086 mol), 1-bromo-4-(trifluoromethyl)benzene (29 mg, 0.00013 mol), sodium tert-butoxide (28 mg, 0.00029 mol), palladium acetate (0.6 mg, 0.000002 mol), and 2-(di-tert-butylphosphino)biphenyl (0.8 mg, 0.000002 mol) in 1,4-dioxane (1.0 mL, 0.013 mol) was heated at 100° C. with stirring for 16 h. LCMS indicated that most of the desired product was oxidized to the ketone so the crude reaction mixture was cooled to −10° C. and 1.0 M of L-Selectride® in tetrahydrofuran (0.2 mL) was added and the mixture was stirred for 20 min. LCMS indicated that the ketone was converted to the alcohol. The crude mixture was purified by prep.-HPLC to afford 5.2 mg of the desired product. LC-MS: 397.2 (M+H)+.

Sources & evidence

ORD record
ord-207d751f20684ae58270d8358a93c362
Source dataset
uspto-grants-2013_10
Patent number
US08563570B2

Reaction notes

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