Hydrochloric Acid → (4-Iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridine-3-yl)methanol

HRID 63935Notes

Reaction equation

HRID 63935 reaction equation
[I:1][C:2]1[C:7]([C:8](OCC)=[O:9])=[C:6]([CH3:13])[N:5]=[C:4]2[S:14][C:15]3[CH2:20][CH2:19][CH2:18][CH2:17][C:16]=3[C:3]=12.[H-].C([Al+]CC(C)C)C(C)C.Cl>C(Cl)Cl>[I:1][C:2]1[C:7]([CH2:8][OH:9])=[C:6]([CH3:13])[N:5]=[C:4]2[S:14][C:15]3[CH2:20][CH2:19][CH2:18][CH2:17][C:16]=3[C:3]=12

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 21225700DiisobutylaluminumhydrideHCID 66603576Ethyl (4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)carboxylate

Product 1

HCID 66784068(4-Iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridine-3-yl)methanolYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of ethyl (4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridine-3-yl)carboxylate (Preparation 5, 260.2 g, 0.65 Mol) in CH2Cl2 (2.0 L) was added 25% (w/w) diisobutyl aluminium hydride (2.0 L, 1.97 Mol) at 5° C. over 1.5 hours under argon. The resulting mixture was allowed to warm to room temperature and stirred for 16 hours. The resulting mixture was diluted with dichloromethane (1.0 L), cooled to 0° C. and 2 M hydrochloric acid (200 mL) was added very carefully. 6M hydrochloric acid was then added until the pH of the aqueous was measured at pH 2. The resulting mixture was stirred vigorously for 1 hour. The precipitate was collected by filtration and the filter-cake was washed with dichloromethane (300 mL) and water (300 mL). The solids were suspended in dichloromethane (250 mL) and 1 M sodium hydroxide solution (400 mL) and stirred vigorously until the solids were free flowing. The solids were collected by filtration, washing the filter-cake with water (200 mL). The filter-cake was concentrated from propan-2-ol (500 mL), methanol (500 mL) and dichloromethane (500 mL) sequentially under reduced pressure to give the title compound as a cream coloured solid (212.3 g, 91%).

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe resulting mixture was stirred vigorously for 1 hour
  3. filtrationThe precipitate was collected by filtration
  4. washthe filter-cake was washed with dichloromethane (300 mL) and water (300 mL)
  5. stirring1 M sodium hydroxide solution (400 mL) and stirred vigorously until the solids
  6. filtrationThe solids were collected by filtration
  7. washwashing the
  8. filtrationfilter-cake with water (200 mL)
  9. concentrationThe filter-cake was concentrated from propan-2-ol (500 mL), methanol (500 mL) and dichloromethane (500 mL) sequentially under reduced pressure

Sources & evidence

ORD record
ord-69968b8900544e538873b32c4ad66a1a
Source dataset
uspto-grants-2016_09
Patent number
US09447116B2

Reaction notes

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