Diisopropylethylamine → N-{5-((1R)-1-Hydroxy-2-{[(1S)-2-hydroxy-1-phenylethyl]amino}ethyl)-2-[(phenylmethyl)oxy]phenyl}-N-(phenylmethyl)methanesulfonamide

HRID 2118347Notes

Reaction equation

HRID 2118347 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[C:9]([N:11]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=1)=[O:4].C(N(CC)C(C)C)(C)C.[C:40]1([C@@H:46]([CH2:48][OH:49])[NH2:47])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C1COCC1>[OH:4][C@H:3]([C:5]1[CH:6]=[CH:7][C:8]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[C:9]([N:11]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=1)[CH2:2][NH:47][C@@H:46]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH2:48][OH:49]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1347972-Amino-2-phenylethan-1-olHCID 86607679N-Benzyl-N-[2-benzyloxy-5-(2-bromoacetyl)phenyl]methanesulfonamide

Product 1

HCID 69120074N-{5-((1R)-1-Hydroxy-2-{[(1S)-2-hydroxy-1-phenylethyl]amino}ethyl)-2-[(phenylmethyl)oxy]phenyl}-N-(phenylmethyl)methanesulfonamideYield 56.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-{5-(bromoacetyl)-2-[(phenylmethyl)oxy]phenyl}-N-(phenylmethyl) methanesulfonamide (570 mg) in THF (15 ml) was treated with N,N-diisopropylethylamine (0.41 ml) and (S)-(+)-2-phenylglycinol (191.8 mg). The mixture was stirred at room temperature for 5 h. The solvent was removed in vacuo and the resulting solid was suspended in dry MeOH (15 ml). The resulting suspension was cooled to 0°, treated with calcium carbonate (359 mg) and stirred for 0.5 h. The reaction mixture was treated with NaBH4 (88.8 mg), portionwise at 0° and was then allowed to warm to room temperature and stirred for 64 h. The mixture was concentrated in vacuo and the residue was partitioned between EtOAc and water. The organic phase was dried (MgSO4) and concentrated in vacuo. The mixture was purified by column chromatography (SPE, gradient 0 to 15% [MeOH-ammonia (10:1)] in DCM) to afford the title compound (360 mg).

Workup

  1. customThe solvent was removed in vacuo
  2. temperatureThe resulting suspension was cooled to 0°
  3. additiontreated with calcium carbonate (359 mg)
  4. stirringstirred for 0.5 h
  5. additionThe reaction mixture was treated with NaBH4 (88.8 mg), portionwise at 0°
  6. temperatureto warm to room temperature
  7. stirringstirred for 64 h
  8. concentrationThe mixture was concentrated in vacuo
  9. customthe residue was partitioned between EtOAc and water
  10. dry with materialThe organic phase was dried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customThe mixture was purified by column chromatography (SPE, gradient 0 to 15% [MeOH-ammonia (10:1)] in DCM)

Sources & evidence

ORD record
ord-e1dab9de7b244434bee11194e07c9539
Source dataset
uspto-grants-2008_10
Patent number
US07442839B2

Reaction notes

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