Citric Acid → HCID 70149816, compound

HRID 1585357Notes

Reaction equation

HRID 1585357 reaction equation
[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[CH2:19][CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1C(=O)N(C)CCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:42][C:43]1[C:50]([CH3:51])=[C:49]([O:52][CH3:53])[CH:48]=[CH:47][C:44]=1[CH2:45]I.C(O)(=O)CC.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.C(OCC)(=O)C.O>[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH2:45][C:44]2[CH:47]=[CH:48][C:49]([O:52][CH3:53])=[C:50]([CH3:51])[C:43]=2[CH3:42])[CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

10

Reactant 6

HCID 311Citric AcidHCID 1032Propionic AcidHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2733832Lithium HexamethyldisilazideHCID 10870461tert-butyl(1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamateHCID 21221126HCID 21221126, compound

Product 1

HCID 70149816HCID 70149816, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.248 g (4.087 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]dihydrofuran-2-(3H)-one (Example 2b)) in 5 ml of abs. THF and 0.823 ml (6.825 mmol) of DMPU is cooled down to -75° C., under argon, and treated dropwise, at an internal temperature of below -70° C. and over the space of approximately 17 min, with 8 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF (Aldrich). After a further 15 min, a solution of 1.128 g (4.087 mmol) of 2,3-dimethyl-4-methoxybenzyl iodide in 3 ml of abs. THF is added dropwise to this mixture within the space of 10 min, and the whole is allowed to react at -75° C. for a further 2 h. For the working-up, the reaction mixture is treated with 1.5 ml of propionic acid and 1.5 ml of water and the temperature is allowed to rise to 0° C. The mixture is poured onto 35 ml of (cold) 10% citric acid solution, and approximately 70 ml of (cold) ethyl acetate is added to this mixture. After stirring for a further 5 min, the phases are separated. The organic phase is washed, in succession, with saline, sat. sodium bicarbonate solution and with saline once again, dried over Na2SO4 and concentrated. The residue which remains after removing the solvent is chromatographed on silica gel (hexane:ethyl acetate, 2:1). The title compound is obtained as a colourless foam. TLC Rf (hexane:ethyl acetate 2:1)=0.37. HPLC tRet =17.83 min (gradient II). FAB-MS (M+H)+ =453. IR(CH2Cl2)=inter alia 3428, 1769, 1712 and 1495 cm-1. 1H-NMR(CDCl3)=inter alia 7.38-7,08 (m, 5H); 6.86 and 6.62 (each d, each 1H); 3.78 (3H); 3.21 and 2.16 (each dxd, each 1H); 2.19 and 2.13 (each s, each 3H); and 1.35 (s, 9H).

Workup

  1. customto react at -75° C. for a further 2 h
  2. customto rise to 0° C
  3. additionis added to this mixture
  4. customthe phases are separated
  5. washThe organic phase is washed, in succession, with saline, sat. sodium bicarbonate solution and with saline once again
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customafter removing the solvent
  9. customis chromatographed on silica gel (hexane:ethyl acetate, 2:1)

Sources & evidence

ORD record
ord-4be3a13e92c74d98b4c1279c0024dd3a
Source dataset
uspto-grants-1999_08
Patent number
US05935976

Reaction notes

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