Triethylamine → 4,5,7,8-Tetrahydro-thieno[2,3-d]azepine-6-carboxylic acid ethyl ester

HRID 627061Notes

Reaction equation

HRID 627061 reaction equation
[S:1]1[C:5]2[CH2:6][CH2:7][NH:8][CH2:9][CH2:10][C:4]=2[CH:3]=[CH:2]1.C(N(CC)CC)C.Cl[C:19]([O:21][CH2:22][CH3:23])=[O:20]>C1COCC1.O>[CH2:22]([O:21][C:19]([N:8]1[CH2:9][CH2:10][C:4]2[CH:3]=[CH:2][S:1][C:5]=2[CH2:6][CH2:7]1)=[O:20])[CH3:23]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 115137774H,5H,6H,7H,8H-thieno[2,3-d]azepine

Product 1

HCID 593025414,5,7,8-Tetrahydro-thieno[2,3-d]azepine-6-carboxylic acid ethyl esterYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5,6,7,8-tetrahydro-4H-thieno[2,3-d]azepine (951 mg, 5.03 mmol) in THF (20 ml) at 0° C. was added triethylamine (1526 mg, 15.09 mmol) and ethyl chloroformate (573 mg, 5.3 mmol). The reaction mixture was warmed to ambient temperature for 4 hours and then diluted with water (100 ml) and extracted with EtOAc (3×75 ml). The combined organic phases were washed with brine (100 ml), dried (MgSO4), and concentrated in vacuo to give the crude product as an oil. Purification by flash chromatography (gradient elution: 0 to 40% EtOAc in hexane) afforded the subtitled compound as an oil; yield 77%. 1H NMR (300 MHz, CDCl3) 6.96 (d, J=5 Hz, 1 H), 6.76 (d, J=5 Hz, 1 H), 4.18 (q, J=7 Hz, 2 H), 3.52-3.78 (m, 4 H), 2.78-3.08 (m, 4 H), 1.28 (t, J=7 Hz, 3 H); MS: ESI (positive): 226 (M+H).

Workup

  1. extractionextracted with EtOAc (3×75 ml)
  2. washThe combined organic phases were washed with brine (100 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto give the crude product as an oil
  6. customPurification
  7. washby flash chromatography (gradient elution: 0 to 40% EtOAc in hexane)

Sources & evidence

ORD record
ord-734a475b57e64bdcba38da2bfb351d67
Source dataset
uspto-grants-2016_04
Patent number
US09309262B2

Reaction notes

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