Dichloromethane → (2R,3S,5S)-oxo-2,3-diphenyl-5-(3-(3-pentyl)benzyl)morpholine

HRID 369810Notes

Reaction equation

HRID 369810 reaction equation
[O:1]=[C:2]1[C@H:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH:15]([CH2:18][CH3:19])[CH2:16][CH3:17])[CH:10]=2)[N:6](C(OC(C)(C)C)=O)[C@@H:5]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@@H:4]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[O:3]1.C(Cl)Cl.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CCOC(C)=O.CCCCCC>[O:1]=[C:2]1[C@H:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH:15]([CH2:16][CH3:17])[CH2:18][CH3:19])[CH:10]=2)[NH:6][C@@H:5]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C@@H:4]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[O:3]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 57256884tert-butyl (2R,3S,5S)-6-oxo-2,3-diphenyl-5-(3-(3-pentyl)benzyl)4-morpholinecarboxylate

Product 1

HCID 57269594(2R,3S,5S)-oxo-2,3-diphenyl-5-(3-(3-pentyl)benzyl)morpholineYield 84%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a 250 mL round bottomed flask equipped with a magnetic stirrer and a nitrogen inlet were added 2.19 g of tert-butyl (2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-(3-pentyl)benzyl)-4-morpholinecarboxylate and 45 mL of anhydrous CH2Cl2. The solution was cooled to 0° C. and was treated with 3.5 mL of TFA. The solution was allowed to warm to RT and was stirred under nitrogen. After 5 h, tlc (SiO2, 9:1 hexane:EtOAc) indicated a trace of starting material and a major new component at Rf =0.42. The reaction mixture was poured into 150 mL of 6% aqueous NaHCO3 and stirred for several minutes. The phases were separated and the aqueous portion was extracted with 3 additional 40 mL portions of CH2Cl2. The extracts were combined with the original CH2Cl2 solution and washed with 5% aqueous NaHCO3 (3×60 mL. The solution was dried over anhydrous MgSO4 and concentrated to give a light tan solid. This material was purified by flash chromatography on silica gel (85:15 hexane:EtOAc) to afford 1.47 g (84%) of (2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-(3-pentyl)benzyl)morpholine as a white crystalline solid. An analytical sample was prepared by recrystallization from EtOH--H2O. Melting point, 96-97° C.

Workup

  1. customTo a 250 mL round bottomed flask equipped with a magnetic stirrer and a nitrogen inlet
  2. temperatureto warm to RT
  3. stirringstirred for several minutes
  4. customThe phases were separated
  5. extractionthe aqueous portion was extracted with 3 additional 40 mL portions of CH2Cl2
  6. washwashed with 5% aqueous NaHCO3 (3×60 mL
  7. dry with materialThe solution was dried over anhydrous MgSO4
  8. concentrationconcentrated
  9. customto give a light tan solid
  10. customThis material was purified by flash chromatography on silica gel (85:15 hexane:EtOAc)

Sources & evidence

ORD record
ord-e9d46b0aad614cf28327b675e2550829
Source dataset
uspto-grants-2000_10
Patent number
US06140100

Reaction notes

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