Hydrochloric Acid → 2-((S)-2-{(R)-4-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester

HRID 2222981Notes

Reaction equation

HRID 2222981 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:45])[C@@H:12]([NH:20][C:21](=[O:44])[C@H:22]([NH2:43])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][C@H:31]([O:38][Si](C)(C)C)[CH2:32][O:33][Si](C)(C)C)=[CH:25][CH:24]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4].C(N(C(C)C)CC)(C)C.[O:55]=[C:56](Cl)OC(Cl)(Cl)Cl.Cl.C(=O)(O)[O-].[Na+]>ClCCl.C(OCC)(=O)C.O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:45])[C@@H:12]([N:20]2[C:21](=[O:44])[C@@H:22]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][C@H:31]([OH:38])[CH2:32][OH:33])=[CH:25][CH:24]=3)[NH:43][C:56]2=[O:55])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 866040572-((S)-2-{(R)-2-amino-2-[4-((S)-2,3-bis-trimethylsilanyloxy-propoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester

Product 1

HCID 586154682-((S)-2-{(R)-4-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl esterYield 52.6%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-((S)-2-{(R)-2-Amino-2-[4-((S)-2,3-bis-trimethylsilanyloxy-propoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester (100 mg, 0.15 mmol) and diisoproylethylamine (0.078 ml, 0.45 mmol) in dichloromethane (2 mL) were added to a solution of diphosgene (0.0143 ml, 0.12 mmol) in dichloromethane (2 mL) over 10 minute at 0° C. The mixture was stirred at 0° C. for 20 minute, diluted with ethyl acetate, washed with saturated sodium bicarbonate, brine and dried over sodium sulfate. Evaporation of solvents gave an oil which was dissolved in tetrahydrofuran (2 mL), treated with 1 N aqueous hydrochloric acid (0.45 ml, 0.45 mmol) and stirred for 3 hours. The reaction was neutralized with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic extracts were washed with brine and dried over magnesium sulfate. The crude product was purified by chromatography over silica gel gradient eluted with 100% ethyl acetate up to 3% v/v methanol in ethyl acetate to give 2-((S)-2-{(R)-4-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester as a solid (35 mg, 42%).

Workup

  1. washwashed with saturated sodium bicarbonate, brine
  2. dry with materialdried over sodium sulfate
  3. customEvaporation of solvents
  4. customgave an oil which
  5. stirringstirred for 3 hours
  6. extractionextracted with ethyl acetate
  7. washThe organic extracts were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customThe crude product was purified by chromatography over silica gel gradient
  10. washeluted with 100% ethyl acetate up to 3% v/v methanol in ethyl acetate

Sources & evidence

ORD record
ord-11b9614a0a3547a79e84c1b3abebb4ee
Source dataset
uspto-grants-2008_05
Patent number
US07371869B2

Reaction notes

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