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

HRID 519354Notes

Reaction equation

HRID 519354 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 boiled 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 was 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 was collected, washed three times with water, and dried in vacuo to afford 117a 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. temperatureunder reflux for 3 h
  2. customExcess thionyl chloride was removed by distillation under reduced pressure
  3. customwas kept below 10° C
  4. stirringThe resulting solution was stirred at 25° C. for 16 h
  5. customMost of the solvent was removed under reduced pressure
  6. temperatureThe residue was chilled in an ice-bath
  7. addition2M KOH solution was introduced slowly
  8. stirringwith stirring
  9. filtrationThe suspension was filtered
  10. customthe solid was collected
  11. washwashed three times with water
  12. customdried in vacuo

Sources & evidence

ORD record
ord-b31b74845a2d4412b0ecf0e3629299d5
Source dataset
uspto-grants-2015_08
Patent number
US09115152B2

Reaction notes

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