L-Phenylalanine → HCID 11306634, compound

HRID 1188755Notes

Reaction equation

HRID 1188755 reaction equation
N[C@H](C(O)=O)CC1C=CC=CC=1.[C:13]([CH:17]1[N:21]([CH3:22])[C:20](=[O:23])[CH2:19][N:18]1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])([CH3:16])([CH3:15])[CH3:14].C(NC(C)C)(C)C.[Li]CCCC.C(OC(N1CC(=O)N(C)[C@@H]1C(C)(C)C)=O)(C)(C)C.Br[CH2:62][C:63]1[CH:68]=[CH:67][C:66]([O:69][CH3:70])=[CH:65][C:64]=1[I:71].[NH4+].[Cl-]>C1COCC1>[C:27]([O:26][C:24]([N:18]1[C@@H:19]([CH2:62][C:63]2[CH:68]=[CH:67][C:66]([O:69][CH3:70])=[CH:65][C:64]=2[I:71])[C:20](=[O:23])[N:21]([CH3:22])[C@@H:17]1[C:13]([CH3:16])([CH3:14])[CH3:15])=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

9

Reactant 7

HCID 6140L-PhenylalanineHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 546472(R)-1-Boc-2-tert-butyl-3-methyl-4-imidazolidinoneHCID 688132(S)-tert-Butyl 2-(tert-butyl)-3-methyl-4-oxoimidazolidine-1-carboxylateHCID 11209601HCID 11209601, compoundHCID 178418339Butyllithium

Product 1

HCID 11306634HCID 11306634, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

This product was obtained using the general procedure reported in the literature [(D. Seebach, E. Dziadulewicz, L. Behrendt, S. Cantoreggi, R. Fitzi, “Synthesis of Nonproteinogenic (R)- or (S)-Amino Acids Analogues of Phenylalanine, Isotopically Labelled and Cyclic Amino Acids from tert-Butyl 2-(tert-Butyl)-3-methyl-4-oxo-1-imidazolidinecarboxylate (Boc-BMI).” Liebigs Ann. Chem., pp 1215-1232 (1989)]. Diisopropylamine (0.9 mL, 6.4 mmol) dissolved in dry THF (5 mL) was cooled to −78° C. under argon and a solution of BuLi (2.5 M in hexane, 2.5 mL) was added drop wise. After 20 min of stirring at −78° C., a solution of (S)-tert-butyl-2-tert-butyl-3-methyl-4-oxoimidazolidine-1-carboxylate (3.0 g, 11.9 mmol) was added drop wise and the reaction mixture was stirred for 30 min at −40° C. A solution of 2-iodo-4-methoxybenzyl bromide (20) (2.08 g, 6.4 mmol) in dry THF (2 mL) was then added drop wise to the reaction mixture. The new reaction mixture was stirred for 2 hours at the same temperature and then poured into a saturated solution of NH4Cl. The product was extracted with EtOAc and the organic layer was washed with NaHCO3 solution followed by brine. The organic phase was dried over anhydrous Na2SO4, filtered and evaporated to produce a yellow oil. Flash chromatographic purification of the oily product provided pure (2S,5S)-tert-Butyl-5-(2′-iodo-4′-methoxybenzyl)-2-tert-butyl-3-methyl-4-oxoimida-zolidine-1-carboxylate (27) as a white solid (743.7 mg, 23%).

Workup

  1. customThis product was obtained
  2. stirringthe reaction mixture was stirred for 30 min at −40° C
  3. stirringThe new reaction mixture was stirred for 2 hours at the same temperature
  4. extractionThe product was extracted with EtOAc
  5. washthe organic layer was washed with NaHCO3 solution
  6. dry with materialThe organic phase was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customto produce a yellow oil
  10. customFlash chromatographic purification of the oily product

Sources & evidence

ORD record
ord-ac79cc7e37224872b356d2629f8fb6e0
Source dataset
uspto-grants-2014_03
Patent number
US08674101B2

Reaction notes

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