Dicyclohexylcarbodiimide → HCID 60142174, compound

HRID 2176755Notes

Reaction equation

HRID 2176755 reaction equation
[N:1]1([CH2:6][CH2:7][C:8]([OH:10])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(N=C=NC2CCCCC2)CCCCC1.[CH3:26][O:27][C:28]([N:30]1[C@@H:38]2[C@@H:33]([C@@:34](O)([C:39]#[C:40][C:41]3[CH:42]=[C:43]([CH3:47])[CH:44]=[CH:45][CH:46]=3)[CH2:35][CH2:36][CH2:37]2)[CH2:32][CH2:31]1)=[O:29]>ClCCl.CN(C)C1C=CN=CC=1>[CH3:26][O:27][C:28]([N:30]1[C@H:38]2[C@H:33]([C@:34]([O:9][C:8](=[O:10])[CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)([C:39]#[C:40][C:41]3[CH:42]=[C:43]([CH3:47])[CH:44]=[CH:45][CH:46]=3)[CH2:35][CH2:36][CH2:37]2)[CH2:32][CH2:31]1)=[O:29]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 55840776234-38-3HCID 68276168(3aS,4R,7aS)-4-hydroxy-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester

Product 1

HCID 60142174HCID 60142174, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

3-Pyrrolidin-1-yl-propionic acid (143 mg, 1.0 mmol) and dicyclohexylcarbodiimide (247 mg, 1.2 mmol) were dissolved in dichloromethane (5 mL). Subsequently, 4-dimethylaminopyridine (97 mg, 0.8 mmol) and (3aS,4R,7aS)-4-hydroxy-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester (250 mg, 0.8 mmol) were added. The resulting suspension was stirred at room temperature (22° C.) for 50 h. The precipitation was then removed by filtration and the clear filtrate was subjected to silica gel flash chromatography [ISCO CombiFlash Companion; 40 g silica gel; methylenechloride/methanol; methanol 0% (4 min), 1% (4 min), 2% (4 min), 2-5% (2 min), 5% (5 min) and 10% (8 min)]. Then, the solvents were evaporated to yield (3aR,4S,7aR)-4-(3-pyrrolidin-1-yl-propionyloxy)-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester (123 mg, 0.28 mmol, 35% yield). MS [M+H]=439; RT=6.122 min (LC-MS Method III). 1H-NMR (600 MHz; DMSO-d6) ppm 1.23 (m, 1H), 1.65 (broad s, 4H), 1.80 to 2.10 (m, 5H), 2.30 (s, 3H), 2.46 (m, 4H), 2.49 (m, 4H), 2.67 (m, 2H), 3.13 (m, 1H), 3.30 (m, 1H), 3.42 (q, 1H), 3.55 (s, 3H), 3.88 (m, 1H), 7.22 (broad s, 2H) and 7.27 (m, 2H).

Workup

  1. customThe precipitation
  2. customwas then removed by filtration
  3. customwas subjected to silica gel flash chromatography [ISCO CombiFlash Companion; 40 g silica gel; methylenechloride/methanol; methanol 0% (4 min), 1% (4 min), 2% (4 min), 2-5% (2 min), 5% (5 min) and 10% (8 min)]
  4. customThen, the solvents were evaporated

Sources & evidence

ORD record
ord-c30ecfa23ffe4a5fae6c96c9bab08dde
Source dataset
uspto-grants-2015_06
Patent number
US09067881B2

Reaction notes

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