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 602856

Reaction equation

HRID 602856 reaction equation
[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

Participants

9

Reactant 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

Product 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 esterYield 56.4%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

(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 agiated 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).

Workup

  1. temperatureto warm to r.t.
  2. waitagiated 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

Sources & evidence

ORD record
ord-7793a4f10ee14ae2b1fa2621295ffeec
Source dataset
uspto-grants-2011_03
Patent number
US07906507B2

Linked notes

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