Triphenylphosphine → (4R,7S)-4-[3-Bromo-4-(4,5-difluoro-2-nitro-benzyloxy)-5-ethoxy-phenyl]-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile

HRID 910766Notes

Reaction equation

[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH2:9][OH:10])=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1.[Br:14][C:15]1[CH:16]=[C:17]([C@H:25]2[C:34]3[C:33](=[O:35])[CH2:32][C@@H:31]([CH2:36][CH2:37][CH3:38])[CH2:30][C:29]=3[NH:28][C:27]([CH3:39])=[C:26]2[C:40]#[N:41])[CH:18]=[C:19]([O:22][CH2:23][CH3:24])[C:20]=1O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Br:14][C:15]1[CH:16]=[C:17]([C@H:25]2[C:34]3[C:33](=[O:35])[CH2:32][C@@H:31]([CH2:36][CH2:37][CH3:38])[CH2:30][C:29]=3[NH:28][C:27]([CH3:39])=[C:26]2[C:40]#[N:41])[CH:18]=[C:19]([O:22][CH2:23][CH3:24])[C:20]=1[O:10][CH2:9][C:5]1[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=1[N+:11]([O-:13])=[O:12]

Participants

Conditions

Temperature: 0 °C

Procedure

To a mixture of (4,5-difluoro-2-nitro-phenyl)-methanol (Example 72f, 5.1 g), (4R,7S)-4-(3-Bromo-5-ethoxy-4-hydroxy-phenyl)-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile (Example 72e, 10.0 g) and polymer-supported triphenylphosphine (13.5 g, 3 mmol/g loading) in THF (500 ml), cooled to 0° C., was added diisopropyl azodicarboxylate (DIAD) (5.3 ml). After 1.5 h, the mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silicagel in heptane/ethyl acetate 4/1-2/3 (v/v) as eluent.

Workup

filtrationthe mixture was filtered
concentrationthe filtrate was concentrated in vacuo
customThe residue was purified by chromatography on silicagel in heptane/ethyl acetate 4/1-2/3 (v/v) as eluent

Sources & evidence

ORD record: ord-f4bb6faa5854453098cceb6a6c585a05
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022218B2

Reaction notes

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