Potassium Carbonate → tert-butyl 5-(N-(2-morpholinoethyl)methylsulfonamido)-thiophene-2-carboxylate

HRID 59749Notes

Reaction equation

HRID 59749 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[S:10][C:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:8][CH:7]=1)(=[O:4])=[O:3].Cl.Cl[CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.C([O-])([O-])=O.[K+].[K+].CS(N(C1SC(C(OC(C)(C)C)=O)=CC=1)S(C)(=O)=O)(=O)=O>CN(C=O)C>[O:25]1[CH2:26][CH2:27][N:22]([CH2:21][CH2:20][N:5]([C:6]2[S:10][C:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:8][CH:7]=2)[S:2]([CH3:1])(=[O:3])=[O:4])[CH2:23][CH2:24]1

Participants

6

Reactant 4

HCID 11430Potassium Carbonate2×HCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)2×HCID 86703851Tert-butyl 5-(methylsulfonamido)thiophene-2-carboxylateHCID 86703852tert-butyl 5-(N-(methylsulfonyl)-methylsulfonamido)thiophene-2-carboxylate

Product 1

HCID 86703853tert-butyl 5-(N-(2-morpholinoethyl)methylsulfonamido)-thiophene-2-carboxylateYield 119.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 5-(methylsulfonamido)thiophene-2-carboxylate (int. 56) (773 mg, 2.79 mmol), 4-(2-chloroethyl)morpholine hydrochloride (778 mg, 4.18 mmol) and K2CO3 (963 mg, 6.97 mmol) in DMF (30 ml) was heated to 80° C. for 6 hours. In parallel a mixture of tert-butyl 5-(N-(methylsulfonyl)methylsulfonamido)thiophene-2-carboxylate (Int. 57) (420 mg, 1.182 mmol), 4-(2-chloroethyl)morpholine hydrochloride (330 mg, 1.772 mmol) and K2CO3 (408 mg, 2.95 mmol) in DMF (15 ml) was heated to 80° C. for 4 hours, stirred at RT overnight and heated to 80° C. for additional 2 hours. The two reaction mixtures were combined and partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc and the combined organic layers were washed several times with brine, dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by flash chromatography on silica gel (petroleum ether/EtOAc=6/4 to EtOAc 100%) to afford tert-butyl 5-(N-(2-morpholinoethyl)methylsulfonamido)-thiophene-2-carboxylate (Int. 58) (1.3 g, 3.33 mmol, MS/ESI+391.0 [MH]+).

Workup

  1. temperaturewas heated to 80° C. for 4 hours
  2. temperatureheated to 80° C. for additional 2 hours
  3. customThe two reaction mixtures
  4. custompartitioned between EtOAc and water
  5. extractionThe aqueous phase was extracted with EtOAc
  6. washthe combined organic layers were washed several times with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe residue was purified by flash chromatography on silica gel (petroleum ether/EtOAc=6/4 to EtOAc 100%)

Sources & evidence

ORD record
ord-a4e95bd6a3984fc58b661a90852fe3e1
Source dataset
uspto-grants-2016_09
Patent number
US09440954B2

Reaction notes

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