Propionic Acid → 5(S)-[1(S)-(Boc-Amino)-2-(p-benzyloxyphenyl)ethyl]-3(R)-[(p-methoxyphenyl)-methyl]dihydrofuran-2-(3H)-one

HRID 1377142Notes

Reaction equation

HRID 1377142 reaction equation
[C:1]([NH:8][C@H:9]([C@H:25]1[O:29][C:28](=[O:30])[CH2:27][CH2:26]1)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[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+].[CH3:41][O:42][C:43]1[CH:50]=[CH:49][C:46]([CH2:47]I)=[CH:45][CH:44]=1.C(O)(=O)CC>C1COCC1.CN1C(=O)N(C)CCC1.O.CCCCCC.C(OCC)(=O)C>[C:1]([NH:8][C@H:9]([C@H:25]1[O:29][C:28](=[O:30])[C@H:27]([CH2:47][C:46]2[CH:49]=[CH:50][C:43]([O:42][CH3:41])=[CH:44][CH:45]=2)[CH2:26]1)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:13][CH:12]=1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

9

Reactant 4

HCID 1032Propionic AcidHCID 2733832Lithium HexamethyldisilazideHCID 11746977p-Methoxybenzyl iodideHCID 54401688[(S)-2-(4-Benzyloxy-phenyl)-1-((S)-5-oxo-tetrahydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl ester

Product 1

HCID 701494225(S)-[1(S)-(Boc-Amino)-2-(p-benzyloxyphenyl)ethyl]-3(R)-[(p-methoxyphenyl)-methyl]dihydrofuran-2-(3H)-one

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-SolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

In analogy with Example 5d), 2.9 g (7.04 mmol) of 5(S)-[1(S)-(Boc-amino)-2-(p-benzyloxy-phenyl)ethyl]dihydrofuran-2-(3H)-one [preparation, see Example 1g)], dissolved in 10.3 ml of THF and 1.2 ml of DMPU, are deprotonated, at -70° C., with 14.1 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF, and alkylated (at from -75° C. to -50° C.), with 2.6 g (10.57 mmol) of p-methoxybenzyl iodide [preparation, see Example 7e)] in 10 ml of THF. Protonation, at -75° C., with 2.6 ml (35.2 mmol) of propionic acid and 2.6 ml of water, extraction and column chromatography (SiO2, hexane/ethyl acetate, 2:1) affords the title compound: TLC Rf (D)=0.48; tRet (II)=18.8 min.

Workup

  1. custom(at from -75° C. to -50° C.)

Sources & evidence

ORD record
ord-e1285e6eea394219b6022a10b7d7a469
Source dataset
uspto-grants-1997_09
Patent number
US05663200

Reaction notes

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