Benzyl chloroformate → (9R,12S,15S)-15-Benzyloxycarbonylamino-12-isopropyl-11,14-dioxo-2-oxa-7-thia-10,13-diaza-bicyclo[15.2.2]henicosa-1(20),17(21),18-triene-9-carboxylic acid methyl ester

HRID 2371318Notes

Reaction equation

HRID 2371318 reaction equation
Cl.[CH3:2][O:3][C:4]([C@H:6]1[NH:24][C:23](=[O:25])[C@H:22]([CH:26]([CH3:28])[CH3:27])[NH:21][C:20](=[O:29])[C@@H:19]([NH2:30])[CH2:18][C:17]2=[CH:31][CH:32]=[C:14]([CH:15]=[CH:16]2)[O:13][CH2:12][CH2:11][CH2:10][CH2:9][S:8][CH2:7]1)=[O:5].Cl[C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35].CCN(C(C)C)C(C)C.CCOC(C)=O.C(Cl)Cl>CN(C=O)C>[CH3:2][O:3][C:4]([C@H:6]1[NH:24][C:23](=[O:25])[C@H:22]([CH:26]([CH3:28])[CH3:27])[NH:21][C:20](=[O:29])[C@@H:19]([NH:30][C:34]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[O:35])[CH2:18][C:17]2=[CH:31][CH:32]=[C:14]([CH:15]=[CH:16]2)[O:13][CH2:12][CH2:11][CH2:10][CH2:9][S:8][CH2:7]1)=[O:5]

Participants

6

Reactant 4

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 21226138Dichloromethane ethylacetateHCID 66846960(9R,12S,15S)-15-Amino-12-isopropyl-11,14-dioxo-2-oxa-7-thia-10,13-diaza-bicyclo-[15.2.2]-henicosa-1(20),17(21),18-triene-9-carboxylic acid methyl ester hydrochloride

Product 1

HCID 66847567(9R,12S,15S)-15-Benzyloxycarbonylamino-12-isopropyl-11,14-dioxo-2-oxa-7-thia-10,13-diaza-bicyclo[15.2.2]henicosa-1(20),17(21),18-triene-9-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Amine 34 (0.200 g, 0.410 mmol) was dissolved in anhydrous DMF (10 mL). Benzyl chloroformate (0.0877 mL, 0.615 mmol) and DIPEA (0.286 mL, 1.64 mmol) were added. The resultant reaction mixture was stirred at rt for 18 h before being partitioned between EtOAc and 1M hydrochloric acid. The aqueous phase was extracted twice more with EtOAc and the combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude material was purified by flash chromatography on silica using a gradient of EtOAc/DCM to yield an off-white solid, 0.0430 g, 18%. Rf=0.44 (30% EtOAc/DCM).

Workup

  1. customThe resultant reaction mixture
  2. custombefore being partitioned between EtOAc and 1M hydrochloric acid
  3. extractionThe aqueous phase was extracted twice more with EtOAc
  4. dry with materialthe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography on silica using a gradient of EtOAc/DCM
  8. customto yield an off-white solid, 0.0430 g, 18%

Sources & evidence

ORD record
ord-bb9ef048950746b780d2501f96d5c81d
Source dataset
uspto-grants-2014_04
Patent number
US08710178B2

Reaction notes

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