Sodium Hydroxide → Tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetic acid

HRID 63938Notes

Reaction equation

HRID 63938 reaction equation
[C:1]([O:5][CH:6]([C:11]1[C:12]([I:25])=[C:13]2[C:20]3[CH2:21][CH2:22][CH2:23][CH2:24][C:19]=3[S:18][C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>O1CCCC1>[C:1]([O:5][CH:6]([C:11]1[C:12]([I:25])=[C:13]2[C:20]3[CH2:21][CH2:22][CH2:23][CH2:24][C:19]=3[S:18][C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66603844HCID 66603844, compound

Product 1

HCID 67606758Tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetic acidYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of Methyl tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetate (Preparation 10, 63.95 g, 135 mmol) in tetrahydrofuran (1 L) and methylated spirit (1 L) was dropwise added aqueous sodium hydroxide (1 M, 811 mL, 811 mmol). The resulting mixture was stirred at 60° C. for 90 minutes and then allowed to cool to room temperature overnight. The volatile solvents were removed in vacuo, and the remaining aqueous residue was diluted with water (400 mL) and extracted with tert-butyl methyl ether (600 mL). The organic layer was washed with water (400 mL) and then cooled on ice. 2 M hydrochloric acid was added to pH 5 and the resulting solids were collected by filtration, washing with water. The solid was dissolved in 2-methyl tetrahydrofuran (300 mL) and stirred for 10 minutes. An aqueous layer had appeared and this was separated. The aqueous layer was extracted with 2-methyl tetrahydrofuran (2×300 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to give the title compound as a pale yellow solid, 54.35 g, in an 88% yield. 1H NMR (400 MHz, CDCl3) δ ppm 1.27 (s, 9 H), 1.81-1.93 (m, 4 H), 2.65 (s, 3 H), 2.76-2.88 (m, 2 H), 3.20-3.27 (m, 2 H), 6.13 (s, 1 H), 9.66 (br s, 1 H).

Workup

  1. temperatureto cool to room temperature overnight
  2. customThe volatile solvents were removed in vacuo
  3. additionthe remaining aqueous residue was diluted with water (400 mL)
  4. extractionextracted with tert-butyl methyl ether (600 mL)
  5. washThe organic layer was washed with water (400 mL)
  6. temperaturecooled on ice
  7. addition2 M hydrochloric acid was added to pH 5
  8. filtrationthe resulting solids were collected by filtration
  9. washwashing with water
  10. dissolutionThe solid was dissolved in 2-methyl tetrahydrofuran (300 mL)
  11. stirringstirred for 10 minutes
  12. customthis was separated
  13. extractionThe aqueous layer was extracted with 2-methyl tetrahydrofuran (2×300 mL)
  14. dry with materialThe combined organic layers were dried over MgSO4
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ff85187fcc6f499dac3b5d41478b8fdb
Source dataset
uspto-grants-2016_09
Patent number
US09447116B2

Reaction notes

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