Phosgene → HCID 58237599, compound

HRID 885331Notes

Reaction equation

HRID 885331 reaction equation
[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][C:13]=2[CH2:19][NH:20][C@@H:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:22][OH:23])[CH:6]=1.C(N(CC)CC)C.[C:38](Cl)(Cl)=[O:39].CCOC(C)=O>C1(C)C=CC=CC=1.[Cl-].[Na+].O>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][C:13]=2[CH2:19][N:20]2[C@@H:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:22][O:23][C:38]2=[O:39])[CH:6]=1

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 58237565HCID 58237565, compound

Product 1

HCID 58237599HCID 58237599, compoundYield 40.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

To {3-(4-Bromo-2-[((S)-2-hydroxy-1-phenyl-ethylamino)-methyl]-phenoxy}-phenyl)-acetic acid methyl ester (0.43 mmol) and triethylamine (0.18 mL, 1.29 mmol) in toluene (1.5 mL) at 0° C. was added phosgene (1.9M in toluene; 0.23 mL, 0.43 mmol). The reaction was stirred for 15 minutes at 0° C., until no starting material was seen by analytical LCMS, and then worked-up with 5% brine and EtOAc. The aqueous layer was extracted twice with EtOAc, and the combined organic layers were dried and concentrated. The residue was purified by silica gel chromatography (20-30% EtOAc in hexanes) to give the desired product (0.086 g).

Workup

  1. extractionThe aqueous layer was extracted twice with EtOAc
  2. customthe combined organic layers were dried
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography (20-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2b7fe0234b5741478cbfd105ac9b7237
Source dataset
uspto-grants-2012_08
Patent number
US08242145B2

Reaction notes

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