Propionic Acid → 5(S)-[1(S)-(Boc-Amino)-2-(p-benzyloxyphenyl)-ethyl]-3(R)-[(4-biphenylyl)methyl]dihydrofuran-2-(3H)-one

HRID 1585376Notes

Reaction equation

HRID 1585376 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+].[C:41]1([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH:46]=[CH:45][C:44]([CH2:47]Br)=[CH:43][CH:42]=1.C(O)(=O)CC>C1COCC1.CN1C(=O)N(C)CCC1.O.C1(C)C=CC=CC=1.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:44]2[CH:45]=[CH:46][C:41]([C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=3)=[CH:42][CH:43]=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

10

Reactant 4

HCID 1032Propionic AcidHCID 2577161,1'-Biphenyl, 4-(bromomethyl)-HCID 2733832Lithium HexamethyldisilazideHCID 54401688[(S)-2-(4-Benzyloxy-phenyl)-1-((S)-5-oxo-tetrahydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl ester

Product 1

HCID 701490905(S)-[1(S)-(Boc-Amino)-2-(p-benzyloxyphenyl)-ethyl]-3(R)-[(4-biphenylyl)methyl]dihydrofuran-2-(3H)-one

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

In analogy with Example 5d), 5.55 g (13.5 mmol) of 5(S)-[1(S)-(Boc-amino)-2-(p-benzyloxyphenyl)ethyl]dihydrofuran-2-(3H)-one [preparation, see Example 1g)], dissolved in 20 ml of THF and 2.3 ml of DMPU, are deprotonated, at -70° C., with 27 ml of a 1 M solution of lithium bis(trimethylsilyl)amide in THF, and alkylated (1 h) with 5.0 g (20.2 mmol) of 4-biphenylylmethyl bromide (Salor, Milwaukee, USA) in 16 ml of THF. Protonating with 5 ml (67.4 mmol) of propionic acid and 5 ml of water, at -75° C., extracting and medium pressure chromatography (gradient: 30-50% ethyl acetate in toluene) results in the title compound: TLC Rf (Q)=0.15; tRet (II)=20.0 min.

Workup

  1. customalkylated (1 h)

Sources & evidence

ORD record
ord-f83b3b8f6a644818b23b812bab3d4c14
Source dataset
uspto-grants-1999_08
Patent number
US05935976

Reaction notes

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