Sodium Carbonate → HCID 178461267, compound

HRID 1190012Notes

Reaction equation

HRID 1190012 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([O-:9])=[O:8])=[C:4]([N:10]([C@H:20]2[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]2)[C:11]([C@H:13]2[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]2)=[O:12])[CH:3]=1.[Li+].[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>[O:28]1[C:32]2([CH2:37][CH2:36][C:35]([C:2]3[S:6][C:5]([C:7]([OH:9])=[O:8])=[C:4]([N:10]([C@H:20]4[CH2:21][CH2:22][C@H:23]([OH:26])[CH2:24][CH2:25]4)[C:11]([C@H:13]4[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]4)=[O:12])[CH:3]=3)=[CH:34][CH2:33]2)[O:31][CH2:30][CH2:29]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 441187651,4-Dioxaspiro[4.5]dec-7-en-8-ylboronic acidHCID 178461266HCID 178461266, compound

Product 1

HCID 178461267HCID 178461267, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of lithium 5-bromo-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methylcyclohexanecarbonyl)-amino]-thiophene-2-carboxylate (498 mg, 1.10 mmol) and 1,4-dioxaspiro[4,5]dec-7-en-8-boronic acid (412 mg, 1.55 mmol) in DMF (6 mL) was added 2M solution of Na2CO3 (3 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 refluxed under nitrogen for 2 h. The mixture was brought to room temperature and filtered through a celite pad washing with EtOAc and H2O. Filtrate was extracted with EtOAc (4×), then aqueous fraction was separated and acidified with 2N HCl till pH 2-3. The mixture was extracted with CH2Cl2 and CH2Cl2-MeOH, organic fraction was dried over Na2SO4 and evaporated to dryness. Crude compound was recrystallized from CH3CN to afford 453 mg (82%) 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 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. temperaturewas refluxed under nitrogen for 2 h
  5. customwas brought to room temperature
  6. filtrationfiltered through a celite pad
  7. washwashing with EtOAc and H2O
  8. extractionFiltrate was extracted with EtOAc (4×)
  9. customaqueous fraction was separated
  10. extractionThe mixture was extracted with CH2Cl2 and CH2Cl2-MeOH, organic fraction
  11. dry with materialwas dried over Na2SO4
  12. customevaporated to dryness
  13. customCrude compound was recrystallized from CH3CN

Sources & evidence

ORD record
ord-bebec9c41ed843c3abc06e9587cc89b0
Source dataset
uspto-grants-2014_03
Patent number
US08674118B2

Reaction notes

Loading…