Methylamine → [1,1-dimethyl-2-(7-methylcarbamoylmethoxy-1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester
Reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:26])([CH3:25])[CH2:10][C:11]1[C:19]2[C:14](=[C:15]([O:20][CH2:21][C:22](O)=[O:23])[CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][NH2:28]>CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([CH3:25])([CH3:26])[CH2:10][C:11]1[C:19]2[C:14](=[C:15]([O:20][CH2:21][C:22](=[O:23])[NH:28][CH3:27])[CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)([CH3:3])([CH3:4])[CH3:2]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of [2-(7-cyanomethoxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (3.8 mmol) is added 2 N NaOH (10.0 mL, 20 mmol). The reaction mixture is reluxed for 2 hours. The reaction mixture is cooled to room temperature, evaporated to about 10 mL, acidified to pH 3.0 with 1 N HCl. The mixture is extracted with ethyl acetate (2×50 mL), the combined organic layer washed with brine and dried (Na2SO4). Evaporation to dryness afford [3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yloxy)-acetic acid (1.3 g, 95%). FDMS m/e=363.2 (M++1). To a solution of [3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yloxy]acetic acid (480 mg, 1.32 mmol) in dimethylformamide (5.0 mL) is added methyl amine (1.52 mL, 1.0 M in tetrahydrofuran, 1.52 mmol) and Bop reagents (670 mg, 1.52 mmol). The reaction mixture is stirred at room temperature for 3 hours before evaporation to dryness. The resulting residue is chromatographed (30% ethyl acetate/hexane) to give 500 mg of [1,1-dimethyl-2-(7-methylcarbamoylmethoxy-1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester (75%). FDMS m/e=375.1 (M++1).
Workup
- customThe resulting residue is chromatographed (30% ethyl acetate/hexane)
Sources & evidence
- ORD record
- ord-6f7c251455c743cbaee5673ee07fb180
- Source dataset
- uspto-grants-2006_08
- Patent number
- US07087635B2
Reaction notes
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