1,4-Dioxane → 5-morpholino-7-oxo-7H-thieno[3,2-b]pyran-3-ylboronic acid

HRID 1042027Notes

Reaction equation

HRID 1042027 reaction equation
Br[C:2]1[C:6]2[O:7][C:8]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[CH:9][C:10](=[O:11])[C:5]=2[S:4][CH:3]=1.O1CCOCC1.C(N(C(C)C)CC)(C)C.CC1(C)C(C)(C)[O:37][BH:36][O:35]1>ClCCl.[Ni](Cl)Cl.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[O:15]1[CH2:16][CH2:17][N:12]([C:8]2[O:7][C:6]3[C:2]([B:36]([OH:37])[OH:35])=[CH:3][S:4][C:5]=3[C:10](=[O:11])[CH:9]=2)[CH2:13][CH2:14]1

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 441811783-Bromo-5-(morpholin-4-yl)-7H-thieno[3,2-b]pyran-7-one

Product 1

HCID 441808545-morpholino-7-oxo-7H-thieno[3,2-b]pyran-3-ylboronic acidYield 109.2%

Reagents, catalysts & solvents 3

HCID 812191,3-Bis(diphenylphosphino)propaneCatalystHCID 2724937Dichloro(1,1'-(1,3-propanediyl)bis(1,1-diphenylphosphine-kappaP))nickelCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
160 °C

Procedure

A 20 mL microwave vial was charged with a magnetic stirring bar, 3-bromo-5-morpholino-7H-thieno[3,2-b]pyran-7-one (103) (1.20 g, 3.80 mmol), 1,3-bis(diphenylphosphino)propane (156 mg, 0.38 mmol), 1,3-bis(diphenylphosphino)propane nickel(II) chloride (205 mg, 0.38 mmol), dioxane (8 mL), diisopropylethylamine (1.98 mL, 11.39 mmol), and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.10 mL, 7.59 mmol). The reaction mixture magnetically stirred and heated via microwave irradiation for 15 minutes at 160° C. Upon cooling to room temperature, the reaction was transferred to a separatory funnel, diluted with dichloromethane (100 mL), and washed three times with saturated aqueous ammonium chloride solution (100 mL). The dichloromethane layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting brown foam was stirred in aqueous hydrochloric acid (1.0M, 100 mL) for 30 minutes, frozen, and lyophilized to give 5-morpholino-7-oxo-7H-thieno[3,2-b]pyran-3-ylboronic acid (69) (1.51 g, 4.15 mmol) as a brown solid.

Workup

  1. additionA 20 mL microwave vial was charged with a magnetic stirring bar
  2. temperatureUpon cooling to room temperature
  3. customthe reaction was transferred to a separatory funnel
  4. washwashed three times with saturated aqueous ammonium chloride solution (100 mL)
  5. dry with materialThe dichloromethane layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. stirringThe resulting brown foam was stirred in aqueous hydrochloric acid (1.0M, 100 mL) for 30 minutes
  9. temperaturefrozen

Sources & evidence

ORD record
ord-0e2c8db39ec64556bf92f46a474437ab
Source dataset
uspto-grants-2013_10
Patent number
US08557807B2

Reaction notes

Loading…