Diphosgene → N-[(5S)-3-cyano-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl]acetamide

HRID 720951Notes

Reaction equation

ClC(OC(Cl)(Cl)Cl)=O.[C:9]([C:12]1[CH:13]=[CH:14][C:15]2[C:21]3[C:22]([O:30][CH3:31])=[C:23]([O:28][CH3:29])[C:24]([O:26][CH3:27])=[CH:25][C:20]=3[CH2:19][CH2:18][C@H:17]([NH:32][C:33](=[O:35])[CH3:34])[C:16]=2[CH:36]=1)(=O)[NH2:10].P(OC)(OC)(OC)=O>>[C:9]([C:12]1[CH:13]=[CH:14][C:15]2[C:21]3[C:22]([O:30][CH3:31])=[C:23]([O:28][CH3:29])[C:24]([O:26][CH3:27])=[CH:25][C:20]=3[CH2:19][CH2:18][C@H:17]([NH:32][C:33](=[O:35])[CH3:34])[C:16]=2[CH:36]=1)#[N:10]

Participants

Reactant 3

HCID 10426Diphosgene

HCID 10541Trimethyl Phosphate

HCID 58658608N-[(55)-3-carbamoyl-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5yl]acetamide

Product 1

HCID 9907187N-[(5S)-3-cyano-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl]acetamideYield 61%

Conditions

Temperature: 60 °C

Procedure

Trichloromethyl chloroformate (0.094 ml; 0.77 mmol) was added in portions at 0° C. to a solution of N-[(5S)-3-carbamoyl-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl]acetamide (0.2 g; 0.484 mmol), (prepared as described for Example 29) and trimethyl phosphate (0.306 ml; 2.6 mmol). The mixture was allowed to warm up and then heated at 60° C. for 5 minutes. The reaction mixture was poured onto ice and stirred. The resulting precipitate was filtered, dried and purified by flash chromatography, eluting with dichloromethane/ethyl acetate (1/1) to give N-[(5S)-3-cyano-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl]acetamide.

Workup

temperatureto warm up
additionThe reaction mixture was poured onto ice
filtrationThe resulting precipitate was filtered
customdried
custompurified by flash chromatography
washeluting with dichloromethane/ethyl acetate (1/1)

Sources & evidence

ORD record: ord-275771af109a4d8d879affde95d3d5e0
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07135502B1

Reaction notes

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