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 1427920

Reaktionsgleichung

Reaktionsgleichung von HRID 1427920
[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

Komponenten

9

Edukt 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

Produkt 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 esterAusbeute 56,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23925IronKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-20 °C

Versuchsvorschrift

(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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-2e394091379c4fb79ac40e909260ac17
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08933222B2

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