Potassium Carbonate → 3-[(2R,5R)-5-Cyclohexyl-2-(3-hydroxy-propyl)-2-methyl-3-oxo-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

HRID 579176Notes

Reaction equation

HRID 579176 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]#[C:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:9]=1Br)=[O:4].C([O-])([O-])=O.[K+].[K+].[CH:23]1([CH:29]2[NH:34][C:33](=[O:35])[C@:32]([CH2:37][CH2:38][CH2:39][OH:40])([CH3:36])[O:31][CH2:30]2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>[Cu]I.O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]#[C:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:9]=1[N:34]1[C@H:29]([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH2:30][O:31][C@@:32]([CH2:37][CH2:38][CH2:39][OH:40])([CH3:36])[C:33]1=[O:35])=[O:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66654511Methyl 3-bromo-5-(3,3-dimethylbut-1-yn-1-yl)thiophene-2-carboxylateHCID 66684415(R)-5-cyclohexyl-2-(3-hydroxy-propyl)-2-methyl-morpholin-3-one

Product 1

HCID 666845993-[(2R,5R)-5-Cyclohexyl-2-(3-hydroxy-propyl)-2-methyl-3-oxo-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl esterYield 26.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a 10 mL vial was added trans-cyclohexane diamine (13.4 mg, 0.12 mmol, 1.0 equiv), 3-bromo-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (70.8 mg, 0.24 mmol, 2.0 equiv), K2CO3 (32.5 mg, 0.24 mmol, 2.0 equiv), CuI (22 mg, 0.12 mmol, 1.0 equiv), (R)-5-cyclohexyl-2-(3-hydroxy-propyl)-2-methyl-morpholin-3-one (30 mg, 0.12 mmol, 1.0 equiv) and 1,4-dioxane (0.4 mL). The mixture was flushed with N2 and stirred at 120° C. for 18 hours. The mixture was filtered through celite and the filtrate was concentrated under vacuum. The residue was purified by silica gel column chromatography, EtOAc/heptane 80% to give product 15 mg (yield 26%).

Workup

  1. customThe mixture was flushed with N2
  2. filtrationThe mixture was filtered through celite
  3. concentrationthe filtrate was concentrated under vacuum
  4. customThe residue was purified by silica gel column chromatography, EtOAc/heptane 80%

Sources & evidence

ORD record
ord-2d922ce395694b0fa1da603409a88f9c
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

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