2-{4-[(Tert-butoxy)carbonyl]piperazin-1-yl}acetic acid → HCID 86702181, compound
Reaction equation
[CH3:1][O:2][C:3]([N:5]1[C@@H:13]2[C@@H:8]([C@@:9]([OH:23])([C:14]#[C:15][C:16]3[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=3)[CH2:10][CH2:11][CH2:12]2)[CH2:7][CH2:6]1)=[O:4].[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][N:34]([CH2:37][C:38](O)=[O:39])[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>>[CH3:1][O:2][C:3]([N:5]1[C@H:13]2[C@H:8]([C@:9]([O:23][C:38](=[O:39])[CH2:37][N:34]3[CH2:33][CH2:32][N:31]([C:29]([O:28][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:30])[CH2:36][CH2:35]3)([C:14]#[C:15][C:16]3[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=3)[CH2:10][CH2:11][CH2:12]2)[CH2:7][CH2:6]1)=[O:4]Participants
Procedure
Synthesis in analogy to the General Method 1 starting from (3aS,4R,7aS)-4-hydroxy-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester and 4-carboxymethyl-piperazine-1-carboxylic acid tert-butyl ester to yield (3aR,4S,7aR)-4-[2-(4-tert-butoxycarbonyl-piperazin-1-yl)-acetoxy]-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester. This NBoc-protected product was then stirred in hydrochloric acid dioxane solution (4M, 10 equiv.) at room temperature for 6 hrs. Subsequently the solvent was removed the residue dissolved in dichloromethane and washed with saturated sodium hydrogencarbonate solution. The organic layer was tried with sodium sulfate, filtrated and evaporated. The crude product was subjected to silica gel flash chromatography (ISCO CombiFlash; dichloromethane/methanol; 100/0 to 95/5) to yield (3aR,4S,7aR)-methyl 4-(2-(piperazin-1-yl)acetoxy)-4-(m-tolylethynyl)octahydro-1H-indole-1-carboxylate. MS [M+H] 440; RT=4.882 min; LCMS Method III
Sources & evidence
- ORD record
- ord-c74941ee2cb3453fae0249d9dbc1611a
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09067881B2
Reaction notes
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