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 1421834Notes

Reaction equation

HRID 1421834 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 (2×), brine and then dried. Removal 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 (2×), brine
  2. customdried
  3. customRemoval of solvent
  4. customgave a yellow gum

Sources & evidence

ORD record
ord-c022202068c240e3ba59c031be04b5f0
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

Loading…