Citric Acid → tert-butyl (1S)-1-{(2R)-5-oxo-4-[4-(2-pyridinyl)benzyl]tetrahydro-2-furanyl}-2-phenylethylcarbamate

HRID 1174282Notes

Reaction equation

HRID 1174282 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C@@H:17]1[O:21][C:20](=[O:22])[CH:19]([C:23](OCC)=O)[CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC[O-].[Na+].BrC[C:34]1[CH:39]=[CH:38][C:37]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=2)=[CH:36][CH:35]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C.O>[O:22]=[C:20]1[O:21][C@@H:17]([C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:18][CH:19]1[CH2:23][C:34]1[CH:35]=[CH:36][C:37]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=2)=[CH:38][CH:39]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 2723922Sodium ethoxideHCID 98875912-(4-(Bromomethyl)phenyl)pyridineHCID 13884421(5R)-5-[(1S)-1-[[(1,1-Dimethylethoxy)carbonyl]amino]-2-phenylethyl]tetrahydro-2-oxo-3-furancarboxylic Acid Ethyl Ester

Product 1

HCID 86599576tert-butyl (1S)-1-{(2R)-5-oxo-4-[4-(2-pyridinyl)benzyl]tetrahydro-2-furanyl}-2-phenylethylcarbamateYield 63.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

A solution of the product from Example 107A (13.3 g, 35.27 mmol) in ethanol (140 mL) at 0° C. was treated with a solution of NaOEt (14.9 mL, 21% in ethanol) and solid 2-[4-(bromomethyl)phenyl]pyridine (12.05 g, 48.59 mmol), stirred at 25° C. for 16 hours, treated with a solution of LiOH monohydrate (8.9 g, 212.11 mmol) in water (35 mL), stirred at 25° C. for 5 hours, cooled to 0° C., adjusted to pH 5 by addition of 10% citric acid and then partitioned between dichloromethane and water. The organic phase was washed with brine and dried over MgSO4, filtered and concentrated. A solution of the concentrate in toluene (1 L) was heated at reflux for 16 hours, cooled and concentrated to give the title compound (10.55 g, 63% yield), which was used without further purification.

Workup

  1. stirringstirred at 25° C. for 5 hours
  2. temperaturecooled to 0° C.
  3. custompartitioned between dichloromethane and water
  4. washThe organic phase was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. concentrationA solution of the concentrate in toluene (1 L)
  9. temperaturewas heated
  10. temperatureat reflux for 16 hours
  11. temperaturecooled
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-43d9cbd8d8a44473824bfec5764208cd
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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