(2S)-2,6-bis((((tert-butoxy)carbonyl)amino))hexanoic acid → (3aR,4S,7aR)-4-((S)-2,6-bis-tert-butoxycarbonylamino-hexanoyloxy)-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester

HRID 2176806Notes

Reaction equation

HRID 2176806 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]([NH:31][C@@H:32]([CH2:36][CH2:37][CH2:38][CH2:39][NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[C:33](O)=[O:34])=[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:33](=[O:34])[C@@H:32]([NH:31][C:29]([O:28][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:30])[CH2:36][CH2:37][CH2:38][CH2:39][NH:40][C:41]([O:43][C:44]([CH3:46])([CH3:47])[CH3:45])=[O:42])([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

3

Reactant 2

HCID 7349648(2S)-2,6-bis((((tert-butoxy)carbonyl)amino))hexanoic acidHCID 68276168(3aS,4R,7aS)-4-hydroxy-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester

Product 1

HCID 86702182(3aR,4S,7aR)-4-((S)-2,6-bis-tert-butoxycarbonylamino-hexanoyloxy)-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester

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 (S)-2,6-bis-tert-butoxycarbonylamino-hexanoic acid to yield (3aR,4S,7aR)-4-((S)-2,6-bis-tert-butoxycarbonylamino-hexanoyloxy)-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-((S)-2,6-diaminohexanoyloxy)-4-(m-tolylethynyl)octahydro-1H-indole-1-carboxylate. MS [M+H] 442; RT=3.992 min; LCMS Method III

Sources & evidence

ORD record
ord-5d1f6989771946cf8c0d9441a277e50b
Source dataset
uspto-grants-2015_06
Patent number
US09067881B2

Reaction notes

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