Ethyl Acetate → (11aS)-1,2,3,10,11,11a-Hexahydro-7-methoxy-8-[3-[[(11aS)-2,3,5,11a-tetrahydro-7-methoxy-5-oxo-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl]oxy]propoxy]-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one

HRID 1816446Notes

Reaction equation

HRID 1816446 reaction equation
C(O[CH:4](SCC)[C@@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:10](=[O:42])[C:11]1[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH2:20][CH2:21][CH2:22][O:23][C:24]2[C:38]([O:39][CH3:40])=[CH:37][C:27]3[C:28](=[O:36])[N:29]4[CH2:35][CH2:34][CH2:33][C@H:30]4[CH2:31][NH:32][C:26]=3[CH:25]=2)=[CH:13][C:12]=1[NH2:41])C.C([O-])([O-])=O.[Ca+2].CCOC(C)=O>CC#N.O.Cl[Hg]Cl>[CH3:18][O:17][C:15]1[C:14]([O:19][CH2:20][CH2:21][CH2:22][O:23][C:24]2[C:38]([O:39][CH3:40])=[CH:37][C:27]3[C:28](=[O:36])[N:29]4[CH2:35][CH2:34][CH2:33][C@H:30]4[CH2:31][NH:32][C:26]=3[CH:25]=2)=[CH:13][C:12]2[N:41]=[CH:4][C@@H:5]3[CH2:9][CH2:8][CH2:7][N:6]3[C:10](=[O:42])[C:11]=2[CH:16]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 10112Calcium CarbonateHCID 86594405HCID 86594405, compound

Product 1

HCID 406087(11aS)-1,2,3,10,11,11a-Hexahydro-7-methoxy-8-[3-[[(11aS)-2,3,5,11a-tetrahydro-7-methoxy-5-oxo-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl]oxy]propoxy]-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one

Reagents, catalysts & solvents 2

HCID 24085Mercuric ChlorideCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A solution of the (2S)-N-{4-[3-(7-Methoxy-(11aS)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5-one-8-yloxy)propoxy]-5-methoxy-2-aminobenzoyl}pyrrolidine-2-carboxaldehyde diethyl thioacetal IV (658 mg, 1 mmol), HgCl2 (794 mg, 2.93 mmol) and CaCO3 (300 mg, 3 mmol) in CH3CN/H2O (4:1, 15 mL) was stirred at room temperature for 12 h until TLC (EtOAc), indicates complete loss of starting material. Then organic layer is evaporated in vacuum and the residue is diluted with EtOAc. To this saturated NaHCO3 was added slowly at room temperature and the mixture is filtered through celite and washed with ethylacetate. The filterate is evaporated in vacuum to get crude 7-Methoxy-8-{3-[7-methoxy-(11aS)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5-one-8-yloxy]propoxy}-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5-one of formula V, which was further purified by column chromatography on silica gel eluting with methanol:EtOAc (2:8).

Workup

  1. customThen organic layer is evaporated in vacuum
  2. additionthe residue is diluted with EtOAc
  3. additionTo this saturated NaHCO3 was added slowly at room temperature
  4. filtrationthe mixture is filtered through celite
  5. washwashed with ethylacetate
  6. customThe filterate is evaporated in vacuum

Sources & evidence

ORD record
ord-c71061f6cf0d4531b0f88727ea3b956b
Source dataset
uspto-grants-2005_04
Patent number
US06884799B2

Reaction notes

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