Hydrochloric Acid → (R)-[4-(2-benzyloxy-1-benzyloxymethyl-ethoxy)-phenyl]-tert-butoxycarbonylamino-acetic acid

HRID 561990Notes

Reaction equation

HRID 561990 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:22]([O:29][CH2:30][CH:31](OS(C1C=C(Cl)C=CC=1Cl)(=O)=O)[CH2:32][O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.Cl>CN(C)C=O.C(OCC)(=O)C.O>[CH2:22]([O:29][CH2:30][CH:31]([CH2:32][O:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[O:19][C:16]1[CH:17]=[CH:18][C:13]([C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C:10]([OH:12])=[O:11])=[CH:14][CH:15]=1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 11821572Boc-4-hydroxy-D-phenylglycineHCID 866322782,5-Dichloro-benzenesulfonic acid 2-benzyloxy-1-benzyloxymethyl-ethyl ester

Product 1

HCID 67001437(R)-[4-(2-benzyloxy-1-benzyloxymethyl-ethoxy)-phenyl]-tert-butoxycarbonylamino-acetic acidYield 80%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (R)-tert-butoxycarbonylamino-(4-hydroxy-phenyl)-acetic acid (1.0 g, 3.74 mmol) in dry N,N-dimethylformamide (20 mL) at 0° C. under an atmosphere of nitrogen was added sodium hydride (60% suspension in mineral oil) (0.33 g, 8.23 mmol) and the mixture stirred at 0° C. for 15 minutes. 2,5-dichloro-benzenesulfonic acid 2-benzyloxy-1-benzyloxymethyl-ethyl ester (2.20 g, 4.57 mmol) was added to the reaction mixture to form a yellow solution which was stirred at ambient temperature for 5 minutes before warming to 100° C. for 10 minutes. The reaction mixture which by now contained a heavy precipitate was cooled to ambient temperature, diluted with ethyl acetate, cooled to 0° C. and treated with an equal volume of water. The stirred mixture was acidified to pH≈4 with 1 M aqueous hydrochloric acid. The organic layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic layers were washed with water (three times), dried over sodium sulfate, filtered through a thin pad of silica gel and concentrated in vacuo to give (R)-[4-(2-benzyloxy-1-benzyloxymethyl-ethoxy)-phenyl]-tert-butoxycarbonylamino-acetic acid (1.20 g, 80%).

Workup

  1. customto form a yellow solution which
  2. stirringwas stirred at ambient temperature for 5 minutes
  3. temperaturebefore warming to 100° C. for 10 minutes
  4. temperaturewas cooled to ambient temperature
  5. temperaturecooled to 0° C.
  6. customThe organic layer was separated
  7. extractionthe aqueous layer extracted with ethyl acetate
  8. washThe combined organic layers were washed with water (three times)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered through a thin pad of silica gel
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-46ac1cf29b8e4575a36b79a6b73c5d47
Source dataset
uspto-grants-2011_11
Patent number
US08063085B2

Reaction notes

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