Acetic Acid → HCID 19374947, compound

HRID 128707Notes

Reaction equation

HRID 128707 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:13][C:12]2[CH2:11][CH2:10][N:9]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:8][C:7]=2[C:6]=1[OH:21])=[O:4].[CH2:22]1[CH2:32]CN2C(=NCCC2)C[CH2:23]1.BrC(C)C.C(O)(=O)C>O1CCCC1.CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:13][C:12]2[CH2:11][CH2:10][N:9]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:8][C:7]=2[C:6]=1[O:21][CH:22]([CH3:32])[CH3:23])=[O:4]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 63582-Bromopropane2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene3×HCID 54699163HCID 54699163, compound

Product 1

HCID 19374947HCID 19374947, compoundYield 68.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
82 °C

Procedure

To a solution of 10.96 g (0,035 mol) of 2-methoxycarbonyl-3-hydroxy-5-tert-butoxycarbonyl-6,7-dihydro-4H-thieno[3,2-c]pyridine (prepared as described in Preparation 6) in 125 mL of tetrahydrofuran were added 8.14 g (0.0535 mol) of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene and 6.55 g (0.053 mol) of 2-bromopropane. The solution was heated at reflux for 4 hours. An additional 3.28 g (0.0266 mol) of 2-bromopropane and 4.07 g (0.0268 mol) of DBU dissolved in 75 mL of DMF were added, and the reaction mixture was stirred at 82° C. for 2.5 hours, cooled to 24° C., and stirred for 3 days. The reaction mixture was added to 550 g of ice water containing 10 mL of glacial acetic acid. The aqueous mixture was extracted four times with 100 mL portions of diethyl ether. The ethereal extracts were combined, washed with saturated aqueous sodium bicarbonate, with water and brine, dried over sodium sulfate, and the solvent was removed by evaporation under reduced pressure to afford 13 g of crystalline 2-methoxycarbonyl-3-isopropoxy-5-tert-butoxycarbonyl-6,7-dihydro-4H-thieno[3,2-c]pyridine, mp 76°-81° C.

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux for 4 hours
  3. additionwere added
  4. temperaturecooled to 24° C.
  5. stirringstirred for 3 days
  6. extractionThe aqueous mixture was extracted four times with 100 mL portions of diethyl ether
  7. washwashed with saturated aqueous sodium bicarbonate, with water and brine
  8. dry with materialdried over sodium sulfate
  9. customthe solvent was removed by evaporation under reduced pressure

Sources & evidence

ORD record
ord-2bad210d76204512add264a27264414e
Source dataset
uspto-grants-1995_11
Patent number
US05464855

Reaction notes

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