Sodium Carbonate → HCID 178499258, compound

HRID 1694467Notes

Reaction equation

HRID 1694467 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7](Br)=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].[O:28]1[C:32]2([CH2:37][CH2:36][C:35](B(O)O)=[CH:34][CH2:33]2)[O:31][CH2:30][CH2:29]1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:35]2[CH2:36][CH2:37][C:32]3([O:31][CH2:30][CH2:29][O:28]3)[CH2:33][CH:34]=2)=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 441187651,4-Dioxaspiro[4.5]dec-7-en-8-ylboronic acidHCID 178499257HCID 178499257, compound

Product 1

HCID 178499258HCID 178499258, compoundYield 92.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromo-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (1.312 g, 2.86 mmol) and 1,4-dioxaspiro[4,5]dec-7-en-8-boronic acid (1.066 g, 4.01 mmol) in DMF (12 mL) was added 2M solution of Na2CO3 (6 mL), and the mixture was deoxygenated by bubbling nitrogen through solution for 10 min. Then Pd(PPh3)4 was added to the mixture, and it was heated at 100° C. for 40 min. The mixture was brought to room temperature, diluted with CH2Cl2, acidified with 3N HCl till pH 2-3, and extracted with EtOAc. Organic fraction was washed with NaHCO3 and brine, dried over Na2SO4, concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel using hexanes-EtOAc gradient to afford 1.368 g (92%) of 5-(1,4-dioxa-spiro[4.5]dec-7-en-8-yl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester as a solid.

Workup

  1. customthe mixture was deoxygenated
  2. customby bubbling nitrogen through solution for 10 min
  3. additionThen Pd(PPh3)4 was added to the mixture, and it
  4. customwas brought to room temperature
  5. additiondiluted with CH2Cl2
  6. extractionextracted with EtOAc
  7. washOrganic fraction was washed with NaHCO3 and brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customthe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-08425a11ba48415eba6598e878d9ea67
Source dataset
uspto-grants-2012_04
Patent number
US08158675B2

Reaction notes

Loading…