Water → N-((9H-Fluoren-9-ylmethoxy)carbonyl)-L-alanine

HRID 2419992Notes

Reaction equation

HRID 2419992 reaction equation
[NH2:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3].Cl[C:8]([O:10][CH2:11][CH:12]1[C:24]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:18]2[C:13]1=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:9].O>C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1>[C:8]([NH:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3])([O:10][CH2:11][CH:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:19]2[C:24]1=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:9]

Participants

6

Reactant 3

HCID 962WaterHCID 5950L-AlanineHCID 343679-Fluorenylmethyl chloroformate

Product 1

HCID 6364642N-((9H-Fluoren-9-ylmethoxy)carbonyl)-L-alanineYield 90.2%

Reagents, catalysts & solvents 2

HCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of L-alanine (1.78g, 20 mmol) in 10% Na2CO3 (53 ml) was added dropwise (within 50 min) with stirring and ice bath cooling a solution of 9-fluorenylmethyl chloroformate (5.17g, 20 mmol) in dioxane (40 ml). The mixture was stirred for 1 hr at 0° and 15 hr at 5°, poured into H2O (1.5 liters) and extracted with ether (2 x). The aqueous layer was cooled in an ice bath, acidified with concentrated HCl to pH 2-3 (white precipitate) and extracted with EtOAc (3 × 500 ml). The organic phase was washed with H2O, dried (MgSO4), filtered, and evaporated. Ether-petroleum ether was added to the residue which crystallized while being kept at 5°. The crude product (5.94g, 95.5%) was recrystallized from methanol-petroleum ether to yield colorless crystals of Fmoc-L-alanine (5.61g, 90.2%), mp 144.5°-145.5° ; [α]D25 = - 11.7° (c 1, CH3OH); tlc, Rf 0.8 (A), 0.3 (B); uv max (CH2Cl2) 267 nm (ε18,950), 290 (5,280), 301 (6,200).

Workup

  1. stirringThe mixture was stirred for 1 hr at 0° and 15 hr at 5°
  2. extractionextracted with ether (2 x)
  3. temperatureThe aqueous layer was cooled in an ice bath
  4. extractionextracted with EtOAc (3 × 500 ml)
  5. washThe organic phase was washed with H2O
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. additionEther-petroleum ether was added to the residue which
  10. customcrystallized
  11. customwhile being kept at 5°
  12. customThe crude product (5.94g, 95.5%) was recrystallized from methanol-petroleum ether

Sources & evidence

ORD record
ord-eaab75f9a9e14a3eab8127b412cfdd07
Source dataset
uspto-grants-1978_08
Patent number
US04108846

Reaction notes

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