Triphenylphosphine → (7S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-tert-butyl ester

HRID 602854

反応式

HRID 602854 の反応式
C[O:2][C:3]([C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][C:10]([OH:18])=[C:11]([N+:15]([O-])=O)[CH:12]=2)[CH2:7][N:6]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ClC1C=C(C=CC=1Cl)C[O:50][C:51](=O)[CH:52]([C:54]1[CH:59]=[CH:58][C:57]([O:60][CH2:61][C:62]2[CH:67]=[CH:66][C:65]([Cl:68])=[C:64]([Cl:69])[CH:63]=2)=[CH:56][CH:55]=1)O.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl.C1COCC1.[Fe].CCOC(C)=O>[C:22]([O:21][C:19]([N:6]1[C@H:5]([C:3]([OH:2])=[O:4])[CH2:14][C:13]2[CH:12]=[C:11]3[C:10]([O:18][CH:52]([C:54]4[CH:59]=[CH:58][C:57]([O:60][CH2:61][C:62]5[CH:67]=[CH:66][C:65]([Cl:68])=[C:64]([Cl:69])[CH:63]=5)=[CH:56][CH:55]=4)[C:51](=[O:50])[NH:15]3)=[CH:9][C:8]=2[CH2:7]1)=[O:20])([CH3:24])([CH3:23])[CH3:25]

参加物

8

反応物 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 66719454(S)-7-hydroxy-6-nitro-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl esterHCID 669225903,4-Dichlorobenzyl 2-(4-((3,4-dichlorobenzyl)oxy)phenyl)-2-hydroxyacetate

生成物 1

HCID 59337459(7S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-tert-butyl ester

試薬・触媒・溶媒 3

HCID 23925Iron触媒HCID 8857Ethyl Acetate溶媒HCID 21919333Tetrahydrofurane dichloromethane溶媒

反応条件

温度
0 °C

実験手順

A solution of (S)-7-hydroxy-6-nitro-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester (3.0 g, 8.5 mmol), resin-bound triphenylphosphine (17 mmol), [4-(3,4-dichloro-benzyloxy)-phenyl]-hydroxy-acetic acid 3,4-dichloro-benzyl ester (13.0 mmol) in DCM-THF (1-1, 80 mL) was cooled to 0° C. To this solution was added DIAD (13.0 mmol) and the mixture was agitated for 10 min at 0° C. and the mixture was slowly allowed to warm up to r.t. and agiated for 16 h. The reaction mixture was filtered, concentrated and the residue passed over a plug of silica-gel hexane-ethyl acetate (9:1). The resulting residue was dissolved in glacial acetic acid (65 mL) and iron powder (170 mmol) added. The resulting mixture was heated at 100° C. for 1 h. The mixture was poured onto water and EtOAc. The organic layer was washed with water, brine, saturated sodium bicarbonate solution and dried over sodium sulfate. The solution was concentrated under reduced pressure to give the desired product. This crude product was purified by silica gel column chromatography using hexanes-ethyl acetate (7:3) to afford (7S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-tert-butyl ester 7-methyl ester (1.6 g). LC-MS (m/z) 614.

後処理

  1. temperatureto warm up to r.t.
  2. waitagiated for 16 h
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated
  5. dissolutionThe resulting residue was dissolved in glacial acetic acid (65 mL)
  6. temperatureThe resulting mixture was heated at 100° C. for 1 h
  7. washThe organic layer was washed with water, brine, saturated sodium bicarbonate solution
  8. dry with materialdried over sodium sulfate
  9. concentrationThe solution was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-5e3e71a6a72644f9a471b8e623ddd4ac
出典データセット
uspto-grants-2011_03
特許番号
US07906507B2

関連ノート

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