Piperidin-4-ol → HCID 121249534, compound

HRID 632822Notes

Reaction equation

Br[C:2]1[C:3]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[OH:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][O:8][C:3]2[C:2]([N:22]3[CH2:23][CH2:24][CH:19]([OH:18])[CH2:20][CH2:21]3)=[CH:7][CH:6]=[CH:5][N:4]=2)=[CH:11][CH:12]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of 3-bromo-2-(4-methoxybenzyloxy)pyridine (7.25 g, 24.65 mmol), 4-hydroxypiperidine (3.74 g, 36.97 mmol), tris(dibenzylideneacetone)dipalladium (451 mg, 0.493 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (614 mg, 0.986 mmol), and sodium-t-butoxide (3.32 g, 34.51 mmol) in anhydrous toluene (90 ml) was heated at 85° C. under nitrogen for 22 hours. The reaction mixture was diluted with ethyl acetate, washed with sat'd NaCl(aq.), dried (MgSO4), filtered, and concentrated. Elution through a flash column (silica gel 60, 230-400 mesh, 1:1 hexanes: EtOAc to 3:7 hexanes: EtOAc) gave the title compound as a brown, viscous oil (4.45 g, 57%).

Workup

washwashed with sat'd NaCl(aq.)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
washElution through a flash column (silica gel 60, 230-400 mesh, 1:1 hexanes: EtOAc to 3:7 hexanes: EtOAc)

Sources & evidence

ORD record: ord-069a437417404f9887f692551abc1698
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321766B1

Reaction notes

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