Methanol → O-benzyl-N-(9-phenyl-9-fluorenyl)-L-serine

HRID 1276701Notes

Reaction equation

HRID 1276701 reaction equation
[NH2:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3]O.Cl[Si](C)(C)C.C(N([CH2:18][CH3:19])CC)C.Br[C:21]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:33]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:27]2[C:22]1=[CH:23][CH:24]=[CH:25][CH:26]=2.[CH3:40][OH:41]>C(Cl)(Cl)Cl.CN(C=O)C.C(Cl)(Cl)Cl>[CH2:40]([O:41][CH2:3][C@@H:2]([C:5]([OH:7])=[O:6])[NH:1][C:21]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:33]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:27]2[C:22]1=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:19]1[CH:18]=[CH:23][CH:22]=[CH:21][CH:33]=1

Participants

8

Reactant 5

HCID 887MethanolHCID 5951L-SerineHCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 2316249-Bromo-9-phenylfluorene

Product 1

HCID 9932688O-benzyl-N-(9-phenyl-9-fluorenyl)-L-serineYield 134.9%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 21754633chloroform N,N-dimethylformamideSolvent

Procedure

To a solution of L-serine (2.34 g, 12 mmol) in CHCl3 /DMF (60 mL, 5/1) was added chlorotrimethylsilane (1.52 mL, 12 mmol) and the mixture was vigorously stirred for 3 h at room temperature. Triethylamine (3.68 mL, 26.4 mmol) was then added slowly to maintain a gentle reflux, and the mixture was stirred for 15 min, after which Pb(NO3)2 (2.66 g, 8.0 mmol) was added, followed by the addition of 9-bromo-9-phenylfluorene (4.36 g, 14.4 mmol) in 30 mL of CHCl3. The mixture was vigorously stirred for 48 h at room temperature, methanol (1.2 mL, 30 mmol) was then added, and the mixture was stirred for an additional 30 min. The resulting mixture was filtered, the filter cake was washed with CHCl3 (2×50 mL), and the dark orange filtrate was evaporated to a residue which was partitioned between ether (200 mL) and aqueous 5% citric acid (60 mL). The aqueous layer was extracted with ether (2×50 mL), the combined organic solution was dried, filtered, and evaporated, and the residue was chromatographed (hexane/ethyl acetate, 8/2; hexane/THF, 6/4) to afford O-benzyl-N-(9-phenyl-9-fluorenyl)-L-serine (4.23 g, 81%) as a white solid.

Workup

  1. temperatureto maintain a gentle reflux
  2. stirringthe mixture was stirred for 15 min
  3. stirringThe mixture was vigorously stirred for 48 h at room temperature
  4. stirringthe mixture was stirred for an additional 30 min
  5. filtrationThe resulting mixture was filtered
  6. washthe filter cake was washed with CHCl3 (2×50 mL)
  7. customthe dark orange filtrate was evaporated to a residue which
  8. customwas partitioned between ether (200 mL) and aqueous 5% citric acid (60 mL)
  9. extractionThe aqueous layer was extracted with ether (2×50 mL)
  10. customthe combined organic solution was dried
  11. filtrationfiltered
  12. customevaporated
  13. customthe residue was chromatographed (hexane/ethyl acetate, 8/2; hexane/THF, 6/4)

Sources & evidence

ORD record
ord-5573e4ec3ef644deabbc7aa71ff9d3fb
Source dataset
uspto-grants-2000_12
Patent number
US06166229

Reaction notes

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