Oxalyl chloride → methyl 7-(4-((4-chlorobenzyloxy)carbamoyl)phenoxy)-6-cyano-3,4-dihydro-2H-chromene-4-carboxylate
Reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:23]([O:25][CH3:26])=[O:24])#[N:2].C(Cl)(=O)C(Cl)=O.[Cl:33][C:34]1[CH:42]=[CH:41][C:37]([CH2:38][O:39][NH2:40])=[CH:36][CH:35]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C=O)C>[Cl:33][C:34]1[CH:42]=[CH:41][C:37]([CH2:38][O:39][NH:40][C:18]([C:17]2[CH:21]=[CH:22][C:14]([O:13][C:12]3[CH:11]=[C:10]4[C:5]([CH:6]([C:23]([O:25][CH3:26])=[O:24])[CH2:7][CH2:8][O:9]4)=[CH:4][C:3]=3[C:1]#[N:2])=[CH:15][CH:16]=2)=[O:20])=[CH:36][CH:35]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
4-(6-cyano-4-(methoxycarbonyl)-3,4-dihydro-2H-chromen-7-yloxy)benzoic acid (from Example 7, Step B) (17 mg, 0.0481 mmol) was diluted with CH2Cl2 (1 mL) followed by the addition of oxalyl chloride in CH2Cl2 (2M in CH2Cl2) (0.0289 mL, 0.0577 mmol) and 1 drop of DMF. This was stirred for 20 minutes followed by the addition of O-(4-chlorobenzyl)hydroxylamine (15.2 mg, 0.0962 mmol) and N,N-diisopropylethylamine (0.0335 mL, 0.192 mmol). After stirring for 30 minutes the reaction was loaded directly onto a Biotage 12i eluting with hexane:ethyl acetate (1:1) to yield the title compound (5 mg, 21.1% yield).
Workup
- stirringAfter stirring for 30 minutes the reaction
- washeluting with hexane:ethyl acetate (1:1)
Sources & evidence
- ORD record
- ord-eb3d873f499145509a28ec904ce8a4ad
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08716498B2
Reaction notes
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