Binap, (A+-)- → N-(2-(2,2,2-Trifluoroethoxy)phenyl)-4-piperidone propylene ketal

HRID 842794Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 50 (1.786 g, 7.00 mmol) and 4-piperidone propylene ketal (2.645 g, 16.82 mmol) in toluene (30 mL) was treated with sodium tert-butoxide (1.88 g, 19.56 mmol), (S)-BINAP (44 mg, 0.07 mmol), and tris(dibenzylideneacetone)dipalladium(0) (32 mg, 0.035 mmol) at room temperature. The mixture was heated in an oil bath (80° C., 3 h). The mixture was diluted with ether and brine. The aqueous layer was extracted with two additional portions of ether and the combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. PCTLC (SiO2, 6 mm, 20% EtOAc-80% hexane) afforded the title compound (51).

Workup

extractionThe aqueous layer was extracted with two additional portions of ether
washthe combined organic extracts were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-fb00847501dd46f78e336a2a664abbff
Source dataset: uspto-grants-2002_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06376503B1

Reaction notes

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