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 612315Notes

Reaction equation

HRID 612315 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 (12.66 g) was hydrolysed in 50% dichloromethane-acetone (80 ml) with toluene-4-sulphonic acid hydrate (10.22 g) in water (25 ml) as described in Example 6 (b). The crude thiol thus prepared (12.942 g), in acetone (50 ml) was treated with (2RS,3SR)-2-bromoacetyl-3-methyltetrahydrofuran (6.57 g) in acetone (20 ml) for 10 min. at room temperature. Then potassium carbonate (2.08 g) was added and stirring continued for 30 min. The solution was diluted with ethyl acetate (200 ml), 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 (10.406 g, 62%); νmax (CH2Cl2) 3405(br), 1780, 1744, 1683 and 1613 cm-1.

Workup

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

Sources & evidence

ORD record
ord-7dab2f8c617b44e59a4eeeba07a6d3f1
Source dataset
uspto-grants-1999_12
Patent number
US06001997

Reaction notes

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