Diisobutylaluminum hydride → HCID 90373394, compound

HRID 930345Notes

Reaction equation

HRID 930345 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:19][S@@:20]([C:22]([CH3:25])([CH3:24])[CH3:23])=[O:21])([CH2:17][F:18])[CH2:9][C:10](OC(C)(C)C)=[O:11])[C:5]([F:26])=[CH:4][CH:3]=1.CC(C[AlH]CC(C)C)C>C(Cl)Cl>[Br:1][C:2]1[N:7]=[C:6]([C@@:8]([NH:19][S@@:20]([C:22]([CH3:24])([CH3:23])[CH3:25])=[O:21])([CH2:9][CH:10]=[O:11])[CH2:17][F:18])[C:5]([F:26])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydride2×HCID 90380071HCID 90380071, compound

Product 1

HCID 90373394HCID 90373394, compoundYield 67.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a 500 mL 3-neck round-bottomed flask equipped with internal temperature monitoring and a magnetic stir bar was added (5)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4-fluorobutanoate (8.90 g, 19.55 mmol) and DCM (200 mL). The solution was cooled to −78° C. and DIBAL-H (Aldrich; 48.9 mL, 48.9 mmol, 1.0 M in hexane) was added over 30 min with the solution running down the side of the flask to precool it. The solution did not go above −74° C. during the addition. After 75 min at −78° C., an additional 5 mL of the DIBALH solution was added. After 10 min the solution was quenched with MeOH (4 mL) dropwise with the MeOH running down the inside of the flask. The solution was allowed to warm to rt and 4 mL of sat NaHCO3 was added. This was stirred for 10 min and then solid Na2SO4 was added (˜20 g). This was stirred for 10 min and then filtered through Celite and the filtercake was washed with DCM. The filtrate was concentrated onto silica. Purification by silica gel chromatography (Gradient: 0.0 to 60% EtOAc/hexane) afforded (R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1-fluoro-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide (5.08 g, 13.25 mmol, 67.8% yield) as a pale yellow oil. MS m/z=383.0 [M+H]+. Calculated for C13H17BrF2N2O2S: 382.0.

Workup

  1. customTo a 500 mL 3-neck round-bottomed flask equipped with internal temperature monitoring and a magnetic stir bar
  2. additionThe solution did not go above −74° C. during the addition
  3. customAfter 10 min the solution was quenched with MeOH (4 mL) dropwise with the MeOH running down the inside of the flask
  4. temperatureto warm to rt
  5. addition4 mL of sat NaHCO3 was added
  6. additionsolid Na2SO4 was added (˜20 g)
  7. stirringThis was stirred for 10 min
  8. filtrationfiltered through Celite
  9. washthe filtercake was washed with DCM
  10. concentrationThe filtrate was concentrated onto silica
  11. customPurification by silica gel chromatography (Gradient: 0.0 to 60% EtOAc/hexane)

Sources & evidence

ORD record
ord-42d7100584fc4c4ea021f4b649d4611e
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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