Cesium carbonate → HCID 178480428, compound

HRID 1190026Notes

Reaction equation

HRID 1190026 reaction equation
[C:1]1([C:7]2[S:11][C:10]([C:12]([OH:14])=[O:13])=[C:9]([N:15]([C:23]([CH:25]3[CH2:30][CH2:29][CH:28]([CH3:31])[CH2:27][CH2:26]3)=[O:24])[CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:39][O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43]>CN(C)C=O>[CH3:43][C:42]([CH3:45])([CH3:44])[C:41]([O:40][CH2:39][O:13][C:12]([C:10]1[S:11][C:7]([C:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=2)=[CH:8][C:9]=1[N:15]([C:23]([C@H:25]1[CH2:30][CH2:29][C@H:28]([CH3:31])[CH2:27][CH2:26]1)=[O:24])[CH:16]1[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]1)=[O:14])=[O:46]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 87885Chloromethyl pivalateHCID 57795367HCID 57795367, compound

Product 1

HCID 178480428HCID 178480428, compoundYield 79.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-cyclohex-1-enyl-3-[(4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid (130 mg, 0.27 mmol) in 5.0 mL of dry dimethylformamide under nitrogen was added cesium carbonate (351 mg, 1.08 mmol) and 2,2-dimethyl-propionic acid chloromethyl ester (45 mg, 0.297 mmol). The mixture was stirred for 120 min at 60° C. The mixture was partitioned between ethyl acetate and water. The EtOAc layer was separated and was washed 3 times with water, dried over Na2SO4. Filtration and removal of the solvent under reduced pressure on a rotary evaporator followed by HPLC purification afforded 120 mg (79%) of 5-cyclohex-1-enyl-3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid 2,2-dimethyl-propionyloxymethyl ester.

Workup

  1. customThe mixture was partitioned between ethyl acetate and water
  2. customThe EtOAc layer was separated
  3. washwas washed 3 times with water
  4. dry with materialdried over Na2SO4
  5. filtrationFiltration and removal of the solvent under reduced pressure
  6. customon a rotary evaporator
  7. customfollowed by HPLC purification

Sources & evidence

ORD record
ord-36eaae9d4ac3469193a671bd04ec54e7
Source dataset
uspto-grants-2014_03
Patent number
US08674118B2

Reaction notes

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