Diisopropylethylamine → n-[2-hydroxy-5-((1r)-1-hydroxy-2-{[(1S)-2-hydroxy-1-phenylethyl]amino}ethyl)phenyl]methanesulfonamide

HRID 749254Notes

Reaction equation

HRID 749254 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([OH:16])=[C:9]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=1)=[O:4].C(N(C(C)C)CC)(C)C.[CH:26]1[CH:31]=[CH:30][C:29]([C@H:32]([NH2:35])[CH2:33][OH:34])=[CH:28][CH:27]=1>CN(C=O)C>[OH:16][C:8]1[CH:7]=[CH:6][C:5]([C@@H:3]([OH:4])[CH2:2][NH:35][C@@H:32]([C:29]2[CH:30]=[CH:31][CH:26]=[CH:27][CH:28]=2)[CH2:33][OH:34])=[CH:10][C:9]=1[NH:11][S:12]([CH3:15])(=[O:14])=[O:13]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1347972-Amino-2-phenylethan-1-olHCID 19073169N-(5-(2-bromoacetyl)-2-hydroxyphenyl)methanesulfonamide

Product 1

HCID 68939213n-[2-hydroxy-5-((1r)-1-hydroxy-2-{[(1S)-2-hydroxy-1-phenylethyl]amino}ethyl)phenyl]methanesulfonamideYield 6.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-[5-(bromoacetyl)-2-hydroxyphenyl]methanesulfonamide (J. Med. Chem. 1967, 10, 462-72) (1.15 g) in dry DMF (30 mL) was treated with diisopropylethylamine (1.06 mL) and (S)-phenylglycinol (474 mg) and the reaction mixture stirred at room temperature for 4 h. The reaction mixture was concentrated in vacuo and the residue re-suspended in methanol (50 mL). The reaction mixture was cooled to 0° C. and treated with CaCl2 (1.27 g). The reaction mixture was stirred at 0° C. for 30 min prior to portionwise addition of NaBH4 (218 mg) ensuring that the temperature did not rise above 10° C. After complete addition the reaction mixture was allowed to warm to room temperature and stirred for a further 74 h. The reaction mixture was concentrated in vacuo and the residue partitioned between EtOAc and water. The organic phase was dried and concentrated in vacuo. The mixture was purified by chromatography (SPE, gradient from DCM to DCM-MeOH—NH3(aq) 100:10:1) afforded the title compound (85 mg). LCMS RT=2.48 min

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. additiontreated with CaCl2 (1.27 g)
  4. stirringThe reaction mixture was stirred at 0° C. for 30 min
  5. additionto portionwise addition of NaBH4 (218 mg)
  6. customdid not rise above 10° C
  7. additionAfter complete addition the reaction mixture
  8. temperatureto warm to room temperature
  9. stirringstirred for a further 74 h
  10. concentrationThe reaction mixture was concentrated in vacuo
  11. customthe residue partitioned between EtOAc and water
  12. customThe organic phase was dried
  13. concentrationconcentrated in vacuo
  14. customThe mixture was purified by chromatography (SPE, gradient from DCM to DCM-MeOH—NH3(aq) 100:10:1)

Sources & evidence

ORD record
ord-0b74101d896e43f790f5ea5b4a78d33b
Source dataset
uspto-grants-2008_07
Patent number
US07402598B2

Reaction notes

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