Benzyl chloroformate → (7S,10S,13S)-13-Benzyloxycarbonylamino-10-isobutyl-9,12-dioxo-2-oxa-8,11-diaza-bicyclo-[13.2.2]nonadeca-1(18),15(19),16-triene-7-carboxylic acid methyl ester

HRID 2371305Notes

Reaction equation

HRID 2371305 reaction equation
Cl.[CH3:2][O:3][C:4]([C@H:6]1[NH:22][C:21](=[O:23])[C@H:20]([CH2:24][CH:25]([CH3:27])[CH3:26])[NH:19][C:18](=[O:28])[C@@H:17]([NH2:29])[CH2:16][C:15]2=[CH:30][CH:31]=[C:12]([CH:13]=[CH:14]2)[O:11][CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5].Cl[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34].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:22][C:21](=[O:23])[C@H:20]([CH2:24][CH:25]([CH3:27])[CH3:26])[NH:19][C:18](=[O:28])[C@@H:17]([NH:29][C:33]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:34])[CH2:16][C:15]2=[CH:30][CH:31]=[C:12]([CH:13]=[CH:14]2)[O:11][CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5]

Participants

6

Reactant 4

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 21226138Dichloromethane ethylacetateHCID 86650239HCID 86650239, compound

Product 1

HCID 44191155(7S,10S,13S)-13-Benzyloxycarbonylamino-10-isobutyl-9,12-dioxo-2-oxa-8,11-diaza-bicyclo-[13.2.2]nonadeca-1(18),15(19),16-triene-7-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Amine 6 (4.00 g, 8.78 mmol) was dissolved in anhydrous DMF (30 mL). Benzyl chloroformate (1.88 mL, 13.2 mmol) and DIPEA (6.11 mL, 35.1 mmol) were added and the reaction mixture was stirred at rt for 18 h before being partitioned between chloroform and 1M hydrochloric acid. The aqueous phase was extracted three more times with chloroform and the combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. Purification was achieved using flash chromatography, eluting with a gradient of 15% EtOAc/DCM to 50% EtOAc/DCM to yield an off-white solid, 2.10 g, 43%. Rf=0.43 (30% EtOAc/DCM).

Workup

  1. custombefore being partitioned between chloroform and 1M hydrochloric acid
  2. extractionThe aqueous phase was extracted three more times with chloroform
  3. dry with materialthe combined organic extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification
  7. washeluting with a gradient of 15% EtOAc/DCM to 50% EtOAc/DCM
  8. customto yield an off-white solid, 2.10 g, 43%

Sources & evidence

ORD record
ord-3f0e2efc4d9f432183a775ac7d642722
Source dataset
uspto-grants-2014_04
Patent number
US08710178B2

Reaction notes

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