Diisobutylaluminumhydride → (3S,5R)-5-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-ol

HRID 20414Notes

Reaction equation

HRID 20414 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[CH2:11]([O:18][C@@H:19]([C@@H:45]1[NH:50][C@@H:49]([CH3:51])[C:48](=[O:52])[O:47][CH2:46]1)[C@@H:20]([N:30]([CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1(C)C=CC=CC=1>[CH2:11]([O:18][C@@H:19]([C@@H:45]1[NH:50][C@@H:49]([CH3:51])[CH:48]([OH:52])[O:47][CH2:46]1)[C@@H:20]([N:30]([CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH2:21][C:22]1[CH:23]=[C:24]([F:29])[CH:25]=[C:26]([F:28])[CH:27]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

4

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 68563893(3S,5R)-5-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-one

Product 1

HCID 68561049(3S,5R)-5-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-olYield 99%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Add diisobutylaluminum hydride (2.48 mL, 2.48 mmol, 1.0 M in toluene) to a solution of (3S,5R)-5-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-one (1.09 g, 1.91 mmol) in dry toluene (20 mL) at −78° C. under nitrogen and stir at this temperature for 15 minutes. Quench by adding methanol (1.0 mL). Add saturated aqueous potassium sodium tartrate (Rochelle salt) and ethyl acetate, warm to room temperature and stir vigorously for 30 minutes. Separate the organic layer and extract the aqueous with ethyl acetate. Combine the organic layers, dry (magnesium sulfate), filter and concentrate to give the desired compound as a mixture of the two possible epimers as a white solid which is used directly in the next step without further purification (1.08 g, 99% yield).

Workup

  1. customQuench
  2. additionby adding methanol (1.0 mL)
  3. stirringstir vigorously for 30 minutes
  4. customSeparate the organic layer
  5. extractionextract the aqueous with ethyl acetate
  6. dry with materialdry (magnesium sulfate)
  7. filtrationfilter
  8. concentrationconcentrate

Sources & evidence

ORD record
ord-bc89a6fa4d9d4e949c7380913325c23b
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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