Sodium Carbonate → (S)-2-tert-Butoxycarbonylamino-3-{(S)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl}-propionic acid methyl ester

HRID 2273393

반응식

HRID 2273393 반응식
[CH3:1][O:2][C:3](=[O:24])[C@@H:4]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[C:8]([N+:13]([O-])=O)[CH:7]=1.C[O:26][C:27](=O)[C@@H:28]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([Cl:45])[CH:39]=2)=[CH:32][CH:31]=1)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.[Fe].CCOC(C)=O>[CH3:1][O:2][C:3](=[O:24])[C@@H:4]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]2[O:12][C@@H:28]([C:30]3[CH:31]=[CH:32][C:33]([O:36][CH2:37][C:38]4[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([Cl:45])[CH:39]=4)=[CH:34][CH:35]=3)[C:27](=[O:26])[NH:13][C:8]=2[CH:7]=1

참가 물질

9

반응물 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 15518593(S)-2-tert-Butoxycarbonylamino-3-(4-hydroxy-3-nitro-phenyl)-propionic acid methyl esterHCID 24965837Methyl (R)-2-(4-((3,4-dichlorobenzyl)oxy)phenyl)-2-hydroxyacetate

생성물 1

HCID 66922588(S)-2-tert-Butoxycarbonylamino-3-{(S)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl}-propionic acid methyl ester수율 56.4%

시약·촉매·용매 3

HCID 23925Iron촉매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

반응 조건

온도
-20 °C

실험 절차

(S)-2-tert-Butoxycarbonylamino-3-(4-hydroxy-3-nitro-phenyl)-propionic acid methyl ester (16.8 mmol) and (R)-[4-(3,4-dichloro-benzyloxy)-phenyl]-hydroxy-acetic acid methyl ester (20.1 mmol) were dissolved in 80 mL of DCM, resin-bound triphenylphosphine (33.6 mmol) added and the mixture cooled to −20° C. To this solution was added DIAD (25.2 mmol) and the mixture was agitated for 30 min at −20° C. The mixture was slowly allowed to warm to r.t. and agitated for 1.5 h. The reaction mixture was filtered and concentrated. The resulting residue was dissolved in glacial acetic acid (60 mL) and heated to 100° C. Iron powder (336 mmol) was added and the resulting mixture heated at 100° C. for 1 h. The mixture was poured onto water and EtOAc. The mixture was brought to ˜pH 7 with sodium carbonate. The organic layer was dried over sodium sulfate and concentrated. The residue was treated with diethyl ether and the resulting solid filtered and washed with diethyl ether to provide (S)-2-tert-Butoxycarbonylamino-3-{(S)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl}-propionic acid methyl ester (5.7 g). LC-MS (m/z) 502 (M-Boc).

후처리

  1. temperatureto warm to r.t.
  2. stirringagitated for 1.5 h
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated
  5. dissolutionThe resulting residue was dissolved in glacial acetic acid (60 mL)
  6. temperatureheated to 100° C
  7. temperaturethe resulting mixture heated at 100° C. for 1 h
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. concentrationconcentrated
  10. additionThe residue was treated with diethyl ether
  11. filtrationthe resulting solid filtered
  12. washwashed with diethyl ether

출처 및 근거

ORD 기록
ord-ae3cd3c75bf24c238f1ae8a78bc99c6d
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09120813B2

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