Water → HCID 68899861, compound

HRID 735375Notes

Reaction equation

HRID 735375 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[F:11][C:12]1[CH:13]=[CH:14][C:15]([C:20]2[CH:29]=[CH:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([S:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)(=[O:32])=[O:31])[CH:26]=3)[CH:21]=2)=[C:16]([CH:19]=1)[C:17]#N.[BH4-].[Na+].[OH2:41]>ClCCl.CO>[F:11][C:12]1[CH:13]=[CH:14][C:15]([C:20]2[CH:29]=[CH:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([S:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)(=[O:32])=[O:31])[CH:26]=3)[CH:21]=2)=[C:16]([CH2:17][OH:41])[CH:19]=1

Participants

7

Reactant 4

HCID 962WaterHCID 4311764Sodium borohydrideHCID 21225700DiisobutylaluminumhydrideHCID 68900138HCID 68900138, compound

Product 1

HCID 68899861HCID 68899861, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of diisobutylaluminium hydride (1M in dichloromethane, 700 μL, 0.70 mmol) was added to 5-fluoro-2-[6-(phenylsulfonyl)-2-naphthyl]benzonitrile (66 mg, 0.17 mmol) in dichloromethane (2 mL) at −78° C. under nitrogen and allowed to warm to 0° C. during 2 hours. It was quenched with ammonium chloride (3 mL), diluted with water (75 mL) and extracted into ethyl acetate (2×50 mL). These extracts were washed with water and brine then dried (MgSO4), filtered and solvent removed in vacuo to give the crude aldehyde as a foam. This foam (67 mg, 0.17 mmol) was suspended in methanol (4 mL) at 0° C. under nitrogen and sodium borohydride (35 mg, 0.92 mmol) added. It was stirred at this temperature for 30 minutes then allowed to return to ambient temperature over 30 minutes. Water (100 mL) was added and the mixture extracted with ethyl acetate (3×30 mL). These extracts were washed with water and brine then dried (MgSO4), filtered and solvent removed in vacuo. Purification by flash column chromatography eluting with a 10-40% ethyl acetate/isohexane gradient gave {5-fluoro-2-[6-(phenylsulfonyl)-2-naphthyl]phenyl}methanol (31 mg, 46%). 1H NMR (500 MHz, CDCl3) δ 8.62 (1H, s), 8.03-8.01 (3H, m), 7.94 (1H, d, J=8.6 Hz), 7.90 (1H, dd, J=1.7, 8.7 Hz), 7.82 (1H, s), 7.60-7.50 (4H, m), 7.35 (1H, dd, J=2.5, 9.6 Hz), 7.29 (1H, dd, J=5.6, 8.4 Hz), 7.11-7.05 (1H, m), 4.60 (2H, d, J=5.1 Hz), 1.67 (1H, t, J=5.5 Hz); m/z (ES+) 393 [MH+].

Workup

  1. customIt was quenched with ammonium chloride (3 mL)
  2. additiondiluted with water (75 mL)
  3. extractionextracted into ethyl acetate (2×50 mL)
  4. washThese extracts were washed with water and brine
  5. dry with materialthen dried (MgSO4)
  6. filtrationfiltered
  7. customsolvent removed in vacuo
  8. customto give the crude aldehyde as a foam
  9. waitto return to ambient temperature over 30 minutes
  10. extractionthe mixture extracted with ethyl acetate (3×30 mL)
  11. washThese extracts were washed with water and brine
  12. dry with materialthen dried (MgSO4)
  13. filtrationfiltered
  14. customsolvent removed in vacuo
  15. customPurification by flash column chromatography
  16. washeluting with a 10-40% ethyl acetate/isohexane gradient

Sources & evidence

ORD record
ord-ac622db38891427295e607e76856be9d
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Reaction notes

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