Acetic acid, azido-, ethyl ester → 2-(2-Azido-2-ethoxycarbonyl-vinyl)-4,5,7,8-tetrahydro-thieno[2,3-d]azepine-6-carboxylic acid ethyl ester

HRID 627063Notes

Reaction equation

HRID 627063 reaction equation
[O-]CC.[Na+].[CH2:5]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[CH:17]=[C:18]([CH:20]=O)[S:19][C:13]=2[CH2:12][CH2:11]1)=[O:9])[CH3:6].[N:22]([CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=[N+:23]=[N-:24]>C(O)C>[CH2:5]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[CH:17]=[C:18]([CH:20]=[C:25]([N:22]=[N+:23]=[N-:24])[C:26]([O:28][CH2:29][CH3:30])=[O:27])[S:19][C:13]=2[CH2:12][CH2:11]1)=[O:9])[CH3:6]

Participants

5

Reactant 3

HCID 69480Acetic acid, azido-, ethyl esterHCID 2723922Sodium ethoxideHCID 904108482-Formyl-4,5,7,8-tetrahydro-thieno[2,3-d]azepine-6-carboxylic acid ethyl ester

Product 1

HCID 1317352752-(2-Azido-2-ethoxycarbonyl-vinyl)-4,5,7,8-tetrahydro-thieno[2,3-d]azepine-6-carboxylic acid ethyl esterYield 44.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of sodium ethoxide in ethanol (21 wt % in EtOH, 8 ml, 21.4 mmol) was diluted with additional ethanol (˜5 ml) and cooled to 0° C. To this solution was added the product from step (c) (4.50 g, 17.76 mmol) and ethyl azidoacetate (25% wt % in EtOH, 11 ml, 21.4 mmol). The reaction mixture was stirred and allowed to warm to RT over 16 hrs. The reaction mixture was then quenched by pouring into saturated aqueous NH4Cl. The aqueous mixture was extracted with Et2O (3×). The combined Et2O extracts were washed with brine, dried (MgSO4), filtered, and solvent evaporated in vacuo to give an orange oil. The crude oil was purified by flash silica-gel chromatography (gradient elution: 0 to 45% EtOAc in hexanes) to give the subtitled compound as a yellow oil (2.9 g). MS: ESI (positive): 365 (M+H).

Workup

  1. temperatureto warm to RT over 16 hrs
  2. customThe reaction mixture was then quenched
  3. additionby pouring into saturated aqueous NH4Cl
  4. extractionThe aqueous mixture was extracted with Et2O (3×)
  5. washThe combined Et2O extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customsolvent evaporated in vacuo
  9. customto give an orange oil
  10. customThe crude oil was purified by flash silica-gel chromatography (gradient elution: 0 to 45% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9cbfe11b97174080a27076d5d3c8122f
Source dataset
uspto-grants-2016_04
Patent number
US09309262B2

Reaction notes

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