Benzyl chloroformate → HCID 66847059, compound

HRID 58368Notes

Reaction equation

HRID 58368 reaction equation
Cl.[CH3:2][O:3][C:4]([C@H:6]1[NH:23][C:22](=[O:24])[C@H:21]([CH2:25][CH:26]([CH3:28])[CH3:27])[NH:20][C:19](=[O:29])[C@@H:18]([NH2:30])[CH2:17][C:16]2=[CH:31][CH:32]=[C:13]([CH:14]=[CH:15]2)[O:12][CH2:11][CH2:10][CH2:9][CH2:8][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:23][C:22](=[O:24])[C@H:21]([CH2:25][CH:26]([CH3:28])[CH3:27])[NH:20][C:19](=[O:29])[C@@H:18]([NH:30][C:34]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[O:35])[CH2:17][C:16]2=[CH:31][CH:32]=[C:13]([CH:14]=[CH:15]2)[O:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5]

Participants

6

Reactant 4

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 21226138Dichloromethane ethylacetateHCID 66847433(8S,11S,14S)-14-Amino-11-isobutyl-10,13-dioxo-2-oxa-9,12-diaza-bicyclo[14.2.2]icosa-1(19),16(20),17-triene-8-carboxylic acid methyl ester hydrochloride

Product 1

HCID 66847059HCID 66847059, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Amine 25 (0.550 g, 1.17 mmol) was dissolved in anhydrous DMF (20 mL). Benzyl chloroformate (0.250 mL, 1.76 mmol) and DIPEA (0.815 mL, 4.68 mmol) were added and the 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, 0.460 g, 69%. Rf=0.32 (30% EtOAc/DCM). m.p. 91-93° C.

Workup

  1. custombefore being partitioned between EtOAc and 1M hydrochloric acid
  2. extractionThe aqueous phase was extracted twice more with EtOAc
  3. dry with materialthe combined organic extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography on silica using a gradient of EtOAc/DCM
  7. customto yield an off-white solid, 0.460 g, 69%

Sources & evidence

ORD record
ord-ba196075723b468c8a5c2fd957450f99
Source dataset
uspto-grants-2016_09
Patent number
US09434762B2

Reaction notes

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