Toluene → HCID 11706498, compound

HRID 32831Notes

Reaction equation

HRID 32831 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:36])[C@@H:12]([NH:21][C:22](=[O:35])[C@H:23]([NH2:34])[C:24]2[CH:33]=[CH:32][C:27]3[O:28][CH2:29][CH2:30][O:31][C:26]=3[CH:25]=2)[C@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[S:8][CH:9]=1)=[O:4].C(N(C(C)C)CC)(C)C.[O:46]=[C:47](Cl)OC(Cl)(Cl)Cl.C1(C)C=CC=CC=1>O1CCCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:36])[C@@H:12]([N:21]2[C:22](=[O:35])[C@@H:23]([C:24]3[CH:33]=[CH:32][C:27]4[O:28][CH2:29][CH2:30][O:31][C:26]=4[CH:25]=3)[NH:34][C:47]2=[O:46])[C@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[S:8][CH:9]=1)=[O:4]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 866033922-{(2S,3S)-2-[(R)-2-amino-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

Product 1

HCID 11706498HCID 11706498, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-{(2S,3S)-2-[(R)-2-amino-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (0.380 g, 0.75 mmol)) and diisopropylethylamine (0.52 mL, 3 mmol) in tetrahydrofuran (7.5 mL) were added to a solution of diphosgene (0.48 mL, 4 mmol) in a mixture of toluene (7.5 mol) and tetrahydrofuran (7.5 mol) over 10 minutes at 0° C. The mixture was stirred at 0° C. for 20 minutes and then diluted with ethyl acetate. The mixture was washed with water, brine and dried (sodium sulfate). Evaporation of the solvents and chromatography of the residue over silica gel gradient eluted with 0.2-1% methanol in dichloromethane gave (2-{(2S,3S)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (0.22 g, 55%).

Workup

  1. washThe mixture was washed with water, brine
  2. dry with materialdried (sodium sulfate)
  3. customEvaporation of the solvents and chromatography of the residue over silica gel gradient
  4. washeluted with 0.2-1% methanol in dichloromethane

Sources & evidence

ORD record
ord-92af6bd4f634404c8fb80224b386afee
Source dataset
uspto-grants-2008_09
Patent number
US07427635B2

Reaction notes

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