Reaction equation
N(C(OC(C)(C)C)=O)[C@H:2]([C:12](O)=O)[CH2:3][O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].Cl.F[C:30]1[CH:35]=[CH:34][C:33]([N:36]2C3C(=CC(I)=CC=3)C=N2)=[CH:32][CH:31]=1>>[C:6]1([CH2:5][O:4][CH2:3][C:2]2[CH:12]=[CH:34][CH:35]=[CH:30][C:31]=2[CH2:32][CH2:33][NH2:36])[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1Participants
Procedure
(αS)-3-Fluoro-β-[[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy]-α-[[(phenylmethoxy)methyl]benzeneethanamine is synthesized in analogy to the sequence previously described in example 1: commercially available Boc-Ser(Bn)-OH is transformed into its Weinreb-amide. Reduction to the aldehyde with LiAlH4, reaction with 3-fluorophenylgrignard, cleavage of the tert.-butyloxycarbonyl protecting group, liberation of the amine from the hydrochloride and etherification with 1-(4-fluorophenyl)-5-iodo-1H-indazole gives the desired amine. This amine (123.3 mg, 0.25 mmol) is dissolved in 10 mL of dichloromethane. Triethylamine (0.084 mL, 0.61 mmol) and 0.028 mL (0.3 mmol) 2-methoxyacetylchloride are added. The reaction mixture is stirred overnight at r.t., then diluted with dichloromethane, washed with water and brine and dried over Na2SO4. After filtration the solvent is evaporated and the residue purified by chromatography (silicagel, eluents: ethyl acetate/hexane). 79.1 mg (55.9%) of the title compound as a mixture of stereoisomers are isolated.
Sources & evidence
- ORD record
- ord-f4d9f73907164af7944f4ebf646578fb
- Source dataset
- uspto-grants-2010_06
- Patent number
- US07728030B2
Linked notes
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