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

HRID 13573

Reaction equation

HRID 13573 reaction equation
[CH3:1][O:2][C:3](=[O:41])[C@@H:4]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:5][C:6]1[CH:7]=[CH:8][C:9]2[O:14][C@@H:13]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=4)=[CH:17][CH:16]=3)[C:12](=[O:31])[NH:11][C:10]=2[CH:32]=1.CO.[C:44]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:41])[C@@H:4]([NH:33][C:34]([O:36][C:37]([CH3:38])([CH3:40])[CH3:39])=[O:35])[CH2:5][C:6]1[CH:7]=[CH:8][C:9]2[O:14][C@@H:13]([C:15]3[CH:16]=[CH:17][C:18]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=4)=[CH:19][CH:20]=3)[C:12](=[O:31])[N:11]([CH3:44])[C:10]=2[CH:32]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 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 ester

Product 1

HCID 66922806(S)-2-tert-Butoxycarbonylamino-3-{(S)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl}-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(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 (9.5 mmol) was dissolved in 60 mL THF-DCM (1:1) and methanol (14.2 mmol) and resin-bound triphenylphosphine (14.2 mmol) was added. The mixture was cooled to 0° C. and DIAD (14.2 mmol) added. 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 purified over silica-gel hexanes-ethyl acetate (8-2) to afford (S)-2-tert-Butoxycarbonylamino-3-{(S)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl}-propionic acid methyl ester. (4.9 g). 1H NMR (400 MHz, CDCl3): 7.51 (d, 1H), 7.44 (d, 1H), 7.31 (m, 2H), 7.25 (m, 1H), 6.96-6.88 (m, 3H), 6.74 (m, 2H), 5.63 (s, 1H), 5.03 (m, 1H), 4.98 (s, 2 h), 4.58 (m, 1 h), 3.70 (s, 3H), 3.41 (s, 3H), 3.05 (m, 2H), 1.28 (s, 9H).

Workup

  1. temperatureto warm up to r.t.
  2. stirringagitated for 16 h
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated
  5. customthe residue purified over silica-gel hexanes-ethyl acetate (8-2)

Sources & evidence

ORD record
ord-3fb17d06473441a9a4a66a61e844f4cd
Source dataset
uspto-grants-2010_06
Patent number
US07727983B2

Linked notes

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