Potassium Carbonate → 4-Methoxybenzyl (2RS)-2-Hydroxy-2-[(3R,4R)-3-phenylacetamido-4-[(2RS, 3SR)-3-methyltetrahYdrofuran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate

HRID 376614Notes

Reaction equation

HRID 376614 reaction equation
[OH:1][CH:2]([N:15]1[C:21](=[O:22])[C@@H:20]2[C@H:16]1[S:17][C:18]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[N:19]2)[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)=[O:4].O.C1(C)C=CC(S(O)(=O)=[O:38])=CC=1.Br[CH2:43][C:44]([CH:46]1[CH:50]([CH3:51])[CH2:49][CH2:48][O:47]1)=[O:45].C(=O)([O-])[O-].[K+].[K+]>ClCCl.CC(C)=O.O.CC(C)=O.C(OCC)(=O)C.C(OCC)(=O)C.CCCCCC>[OH:1][CH:2]([N:15]1[C@H:16]([S:17][CH2:43][C:44]([CH:46]2[CH:50]([CH3:51])[CH2:49][CH2:48][O:47]2)=[O:45])[C@H:20]([NH:19][C:18](=[O:38])[CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:21]1=[O:22])[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)=[O:4]

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 18780092(2RS,3SR)-2-bromoacetyl-3-methyltetrahydrofuranHCID 536561234-Methoxybenzyl (RS)-2-hydroxy-2-[(lR,5R)-3-benzyl-4-thia-2,6-diazabicyclo[3.2.0)hept-2-en-7-on-6-yl]acetate

Product 1

HCID 867549534-Methoxybenzyl (2RS)-2-Hydroxy-2-[(3R,4R)-3-phenylacetamido-4-[(2RS, 3SR)-3-methyltetrahYdrofuran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetateYield 62%

Reagents, catalysts & solvents 5

HCID 180AcetoneSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolventHCID 21584124Propan-2-one--dichloromethane (1/1)Solvent

Procedure

4-Methoxybenzyl (2RS) -2-hydroxy-2-[(1R, 5R)-3-benzyl-4-thia-2,6-diazabicyclo[3.2.0]hept-2-en-7-on-6-yl]acetate (12.66g) was hydrolysed in 50% dichloromethane-acetone (80ml) with toluene-4-sulphonic acid hydrate (10.22g) in water (25ml) as described in Example 6(b). The crude thiol thus prepared (12.942g), in acetone (50ml) was treated with (2RS,3SR)-2-bromoacetyl-3-methyltetrahydrofuran (6.57g) in acetone (20ml) for 10min. at room temperature. Then potassium carbonate (2.08g) was added and stirring continued for 30min. The solution was diluted with ethyl acetate (200ml), washed with water (2x), brine and then dried. Remvoal of solvent gave a yellow gum. Flash chromatography on silica gel eluting with 50, 60, 70, 80 and then 90% ethyl acetate-hexane afforded the title compound as a pale yellow foam (10.406g, 62%); vmax (CH2Cl2) 3405(br), 1780, 1744, 1683 and 1613cm-1.

Workup

  1. washwashed with water (2x), brine
  2. customdried
  3. customRemvoal of solvent gave a yellow gum

Sources & evidence

ORD record
ord-a59ee7f3a32a463394b6ffe0d230dc87
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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