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 2369113

반응식

HRID 2369113 반응식
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]

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 3

HCID 23925Iron촉매HCID 8857Ethyl Acetate용매HCID 21919333Tetrahydrofurane dichloromethane용매

반응 조건

온도
0 °C

실험 절차

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 agitated for 16 h. The reaction mixture was filtered, concentrated and the residue passed over a plug of silica-gel hexanes-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.

후처리

  1. temperatureto warm up to r.t.
  2. stirringagitated 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

출처 및 근거

ORD 기록
ord-f575900a607d492d855386c491e23dc4
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08703766B2

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