Citric Acid → HCID 70149726, compound

HRID 2394147Notes

Reaction equation

HRID 2394147 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][O:43][C:44]1[CH:51]=[CH:50][CH:49]=[CH:48][C:45]=1[CH2:46]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]([CH2:46][C:45]2[CH:48]=[CH:49][CH:50]=[CH:51][C:44]=2[O:43][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 15876972HCID 15876972, compound

Product 1

HCID 70149726HCID 70149726, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1 g (3.275 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]dihydrofuran-2-(3H)-one [Example 2b)] in 4 ml of abs. THF and 0.66 ml of DMPU (1.67 equivalents) is cooled down to -75° C., under argon, and treated dropwise, at an internal temperature of below -70° C. and over the space of 30 min, with 6.42 ml (1.96 equivalents) of a 1M solution of lithium bis(trimethylsilyl)amide in THF (Aldrich, Steinheim, FRG). After a further 15 min, 812 mg (3.275 mmol) of 2-methoxybenzyl iodide, dissolved in 2 ml of THF, are added dropwise to this mixture within the space of 10 min, and the whole is allowed to react at -70° C. for 2 h. 1.22 ml of propionic acid and 1.22 ml of water are subsequently added to this solution, and the temperature is allowed to rise to 0° C. The reaction mixture is diluted with 50 ml of (cold) ethyl acetate and stirred, for 5 min, with 20 ml of (cold) 10% citric acid, and, after that, the phases are separated. The organic phase is washed, in succession, with saline, sat. sodium bicarbonate solution and once again with saline, dried over Na2SO4 and concentrated. The title compound is isolated by means of flash chromatography on silica gel (hexane:ethyl acetate=3:1). TLC Rf (hexane:ethyl acetate=3:1)=0.54.-MS M+ =455.-HPLC tRet =17.09 min (gradient II).-IR(CH2Cl2)=inter alia 3429, 1769, 1712, and 1495 cm-1.-1H-NMR(CDCl3)=inter alia 7.38-7.13/m (5H); 7.20/d (1H); 7.08/d (1H); 6.87/t (1H); 6.81/d (1H); 3.74/s (3H); 1.34/s (9H).

Workup

  1. additionare added dropwise to this mixture within the space of 10 min
  2. customto react at -70° C. for 2 h
  3. customto rise to 0° C
  4. customafter that, the phases are separated
  5. washThe organic phase is washed, in succession, with saline, sat. sodium bicarbonate solution and once again with saline
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2ab3ef1a6d9b4ecdbee66ff28b81898e
Source dataset
uspto-grants-1998_09
Patent number
US05807891

Reaction notes

Loading…