Tert-Butylamine → N-tert-Butyl-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

HRID 592800Notes

Reaction equation

HRID 592800 reaction equation
[S:1]1[C:5]([C:6]([OH:8])=O)=[CH:4][C:3]2[CH2:9][CH2:10][CH2:11][CH2:12][C:2]1=2.S(Cl)(Cl)=O.[C:17]([NH2:21])([CH3:20])([CH3:19])[CH3:18]>ClCCl>[C:17]([NH:21][C:6]([C:5]1[S:1][C:2]2[CH2:12][CH2:11][CH2:10][CH2:9][C:3]=2[CH:4]=1)=[O:8])([CH3:20])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 6385Tert-ButylamineHCID 24386Thionyl ChlorideHCID 20634434,5,6,7-Tetrahydro-1-benzothiophene-2-carboxylic acid

Product 1

HCID 4806824N-tert-Butyl-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideYield 88.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxylic acid (500 g, 2.75 mol, 1.0 equiv) and thionyl chloride (655 g, 5.5 mol, 2.0 equiv) was heated under reflux for 3 h. Excess thionyl chloride was removed by distillation under reduced pressure. The residue was taken up in dichloromethane (1.0 L) and a solution of tert-butylamine (402 g, 5.5 mol, 2.0 equiv) in dichloromethane (500 mL) was added with stirring while the temperature of the mixture being kept below 10° C. The resulting solution was stirred at 25° C. for 16 h. Most of the solvent was removed under reduced pressure. The residue was chilled in an ice-bath and 2M KOH solution was introduced slowly to adjust the pH to 11 with stirring. The suspension was filtered and the solid collected, washed three times with water, and dried in vacuum to afford 191a as a white solid (580 g, 80%, over two steps). MS: [M+H]+ 238. 1H NMR (500 MHz, CDCl3) δ 7.02 (s, 1H), 5.77 (s, 1H), 2.65 (t, J=6.0 Hz, 1H), 2.47 (t, J=6.0 Hz, 1H), 1.74-1.70 (m, 4H), 1.35 (s, 9H).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3 h
  3. customExcess thionyl chloride was removed by distillation under reduced pressure
  4. custombeing kept below 10° C
  5. stirringThe resulting solution was stirred at 25° C. for 16 h
  6. customMost of the solvent was removed under reduced pressure
  7. temperatureThe residue was chilled in an ice-bath
  8. addition2M KOH solution was introduced slowly
  9. stirringwith stirring
  10. filtrationThe suspension was filtered
  11. customthe solid collected
  12. washwashed three times with water
  13. customdried in vacuum

Sources & evidence

ORD record
ord-dccfdeb104254c5cb56a64fb49a7cb75
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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