Tributylphosphine → 4-{4-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-phenyl}-5,6-dihydro-2H-pyridine-1,3-dicarboxylic Acid 1-tert-butyl Ester 3-methyl Ester

HRID 2428182Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[CH2:6][N:7]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:8][CH2:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)=[O:4].[Cl:25][C:26]1[C:31]([F:32])=[CH:30][CH:29]=[C:28]([F:33])[C:27]=1[C:34]1[CH:38]=[C:37]([CH2:39]O)[O:36][N:35]=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1.P(CCCC)(CCCC)CCCC>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[CH2:6][N:7]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:8][CH2:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:39][C:37]2[O:36][N:35]=[C:34]([C:27]3[C:28]([F:33])=[CH:29][CH:30]=[C:31]([F:32])[C:26]=3[Cl:25])[CH:38]=2)=[CH:13][CH:12]=1)=[O:4]

Participants

Conditions

Temperature: 80 °C

Procedure

To a sol. of compound B2 (10.0 g, 30 mmol) and [3-(2-chloro-3,6-difluoro-phenyl)-isoxazol-5-yl]-methanol (8.84 g, 30 mmol) in toluene (60 mL) were added ADDP (15.1 g, 60 mmol) and PBu3 (90%, 30.0 mL; 108 mmol). The mixture was stirred for 2 h at 80° C., and was allowed to cool to rt. The solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 1:4→EtOAc) yielded the title compound (8.64 g, 51%). LC-MS: tR=1.15 min; ES+: 561.25.

Workup

temperatureto cool to rt
customThe solvents were removed under reduced pressure
customPurification of the residue by FC (EtOAc/heptane 1:4→EtOAc)

Sources & evidence

ORD record: ord-2ff0b387234140d7b5c116a8ca753f81
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07968720B2

Reaction notes

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