Propionic Acid → Acetate

HRID 2394095Notes

Reaction equation

HRID 2394095 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].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:33]1([CH2:39][CH2:40][C:41]2[CH:48]=[CH:47][C:44]([CH2:45]Br)=[CH:43][CH:42]=2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(O)(=O)CC>C1COCC1.C(OCC)(=O)C.O.CN1C(=O)N(C)CCC1>[C:20]([O-:22])(=[O:21])[CH3:19].[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:41]([CH2:40][CH2:39][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:42][CH:43]=2)[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 4

HCID 1032Propionic AcidHCID 2733832Lithium HexamethyldisilazideHCID 10870461tert-butyl(1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamateHCID 12941339HCID 12941339, compound

Product 2

HCID 175AcetateHCID 70150597HCID 70150597, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
0 °C

Procedure

A solution of 4.4 g (14.53 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]dihydrofuran-2-(3H)-one [preparation, see Example 2b)] in 21.4 ml of abs. THF and 2.4 ml of DMPU is treated, at -75° C. and under an N2 atmosphere, with 28 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF (Aldrich, Steinheim, FRG), and the mixture is subsequently stirred at this temperature for 15 min. A solution of 6.0 g (approximately 80%, 17.5 mmol) of p-(2-phenylethyl)benzyl bromide in 5.4 ml of abs. THF is then added dropwise, and this mixture is thoroughly stirred at -70° C. for 30 min. 5.4 ml of propionic acid are then added at -75° C., followed by 5.4 ml of water. The mixture is warmed to 0° C. and diluted with 150 ml of ethyl acetate; this mixture is then washed with 80 ml of a 10% solution of citric acid, with sat. sodium bicarbonate solution and with saline. The aqueous phases are reextracted 2× with ethyl acetate, and the organic phases are dried over sodium sulfate and evaporated. Column chromatography (SiO2, hexanelethyl acetate, 3:1) yields the pure title compound: TLC Rf (E)=0.27; tRet (II)=20.8 min; FAB-MS (M-Buten+H)+ =444.

Workup

  1. stirringthis mixture is thoroughly stirred at -70° C. for 30 min
  2. washthis mixture is then washed with 80 ml of a 10% solution of citric acid, with sat. sodium bicarbonate solution and with saline
  3. dry with materialthe organic phases are dried over sodium sulfate
  4. customevaporated

Sources & evidence

ORD record
ord-1c1ce8ae51d641cc9f9ef2c05f394725
Source dataset
uspto-grants-1998_09
Patent number
US05807891

Reaction notes

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