Succinate → tert-Butyl ((2S,4S,5S)-5-(2-(2,6-dimethylphenoxy)acetamido)-4-hydroxy-1,6-diphenylhexan-2-yl)carbamate

HRID 1594641Notes

Reaction equation

HRID 1594641 reaction equation
[NH2:1][C@H:2]([C@@H:10]([OH:28])[CH2:11][C@@H:12]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C([O-])(=O)CCC([O-])=O.C([O-])(O)=O.[Na+].[CH3:42][C:43]1[CH:53]=[CH:52][CH:51]=[C:50]([CH3:54])[C:44]=1[O:45][CH2:46][C:47](Cl)=[O:48]>CCOC(C)=O.O>[CH3:42][C:43]1[CH:53]=[CH:52][CH:51]=[C:50]([CH3:54])[C:44]=1[O:45][CH2:46][C:47]([NH:1][C@H:2]([C@@H:10]([OH:28])[CH2:11][C@@H:12]([NH:20][C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)=[O:48]

Participants

7

Reactant 4

HCID 160419SuccinateHCID 516892Sodium BicarbonateHCID 119979265-tert-Butyloxycarbonylamino-2-amino-3-hydroxy-1,6-diphenylhexane, (2S,3S,5S)-HCID 12353505(2,6-Dimethylphenoxy)acetyl Chloride

Product 1

HCID 45039081tert-Butyl ((2S,4S,5S)-5-(2-(2,6-dimethylphenoxy)acetamido)-4-hydroxy-1,6-diphenylhexan-2-yl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Oxallyl chloride (36.3 ml, 0.42 mol) was added to a slurry of 2-6 dimethylphenoxyacetic acid (50 g, 0.28 mol) in 500 ml toluene followed by addition of 5 drops of DMF and stirred at room temperature for 30 min, then at 55° C. for 1.5 hours. The toluene was removed on a rotary evaporator and remaining volatiles were removed in vacuo to afford 2,6-dimethylphenoxyacetyl chloride as an amber oil, 55 grams, 100%. [2S,3S,5S]-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane×0.5 succinate (111.9 g, 0.25 mol) was charged to a 2 L, 3-necked round-bottomed flask with mechanical stirring. NaHCO3 (106 9, 1.26 mol), 600 ml H2O and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 min of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted with EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgSO4, filtered and concentrated to provide the desired product as a white solid.

Workup

  1. dissolutionwere dissolved (15 minutes)
  2. stirringStirring
  3. stirringAfter 30 min of stirring
  4. customwere consumed (HPLC analysis)
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc
  7. washwashed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-222e5d83b0374ad49b623c06a1e5c75f
Source dataset
uspto-grants-2001_09
Patent number
US06284767B1

Reaction notes

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