Diisobutylaluminumhydride → N-(4-(hydroxymethyl)-2-iodo-5-(methylthio)phenyl)methanesulfonamide

HRID 1051828Notes

Reaction equation

HRID 1051828 reaction equation
[I:1][C:2]1[C:3]([NH:15][S:16]([CH3:19])(=[O:18])=[O:17])=[CH:4][C:5]([S:13][CH3:14])=[C:6]([CH:12]=1)[C:7](OCC)=[O:8].[H-].C([Al+]CC(C)C)C(C)C>C1(C)C=CC=CC=1>[OH:8][CH2:7][C:6]1[C:5]([S:13][CH3:14])=[CH:4][C:3]([NH:15][S:16]([CH3:19])(=[O:17])=[O:18])=[C:2]([I:1])[CH:12]=1

Participants

4

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 89815004Ethyl 5-iodo-4-(methylsulfonamido)-2-(methylthio)benzoate

Product 1

HCID 89814728N-(4-(hydroxymethyl)-2-iodo-5-(methylthio)phenyl)methanesulfonamideYield 80%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 5-iodo-4-(methylsulfonamido)-2-(methylthio)benzoate (crude, from step 2) in dry toluene (200 mL) at 0° C. was added diisobutylaluminium hydride (1.0 M in toluene, 100 mL, 100 mmol) slowly. After addition, the mixture was stirred at 0° C. for 3 h and quenched with methanol/H2O (1/1). The reaction mixture was poured into a vigorously stirred solution of potassium sodium tartrate (1M, 300 mL) and stirred vigorously for 2 h, after which time it settled to two clear phases. The organic layer was separated, and the aq layer was extracted with EtOAc (3×200 mL). The combined organic solution was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-40% EtOAc/Hexanes) afford N-(4-(hydroxymethyl)-2-iodo-5-(methylthio)phenyl)methanesulfonamide (11.9 g, 80% yield for two steps). LC-MS m/z 356 [M+H]+. 1H NMR (400 MHz, CDCl3): δ 7.82 (s, 1H), 7.49 (s, 1H), 4.67 (s, 2H), 2.99 (s, 3H), 2.50 (s, 3H).

Workup

  1. additionAfter addition
  2. customquenched with methanol/H2O (1/1)
  3. additionThe reaction mixture was poured into a vigorously stirred solution of potassium sodium tartrate (1M, 300 mL)
  4. stirringstirred vigorously for 2 h
  5. customThe organic layer was separated
  6. extractionthe aq layer was extracted with EtOAc (3×200 mL)
  7. washThe combined organic solution was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by silica gel chromatography (0-40% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-e7dfdd653ba746b88e30dcb676883095
Source dataset
uspto-grants-2016_07
Patent number
US09388190B2

Reaction notes

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