Toluene → HCID 68560852, compound

HRID 20410Notes

Reaction equation

HRID 20410 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[C:11]([O:15][C:16]([N:18]1[C@@H:23]([C@@H:24]([O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[C@@H:25]([N:35]([CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:26][C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=2)[CH2:22][O:21][C:20](=[O:58])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C1(C)C=CC=CC=1.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C(OCC)(=O)C>[C:11]([O:15][C:16]([N:18]1[CH:23]([C@@H:24]([O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[C@@H:25]([N:35]([CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:43][C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:26][C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=2)[CH2:22][O:21][C@@H:20]([OH:58])[CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 1140TolueneHCID 9855836Potassium sodium tartarateHCID 21225700DiisobutylaluminumhydrideHCID 68560976HCID 68560976, compound

Product 1

HCID 68560852HCID 68560852, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Add diisobutylaluminum hydride (1.4 mL, 1.37 mmol, 1.0 M in toluene) to a solution of (R)-5-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-2-oxomorpholine-4-carboxylic acid tert-butyl ester (0.75 g, 1.1 mmol) in of dry toluene (15 mL) at −78° C. under nitrogen and stir at this temperature for 2 hours (Monitor by TLC). Add methanol to quench the reaction (1.0 mL), then 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 and dry (magnesium sulfate), filter and concentrate to give the desired compound as a mixture of the two possible isomers as a white solid and used in the next step without further purification (0.75 g).

Workup

  1. customAdd methanol to quench
  2. customthe reaction (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-b31ce11ca6ca4bc793ecdabf03018862
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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