p-Toluenesulfonic acid → 4-methoxybenzyl (2RS)-2-hydroxy-2-[(3R,4R)-4-mercapto-3-phenylacetamidoazetidin-2-on-1-yl]acetate

HRID 1421821Notes

Reaction equation

HRID 1421821 reaction equation
C1(C)C=CC(S(O)(=O)=[O:8])=CC=1.[OH:12][CH:13]([N:26]1[C:32](=[O:33])[C@@H:31]2[C@H:27]1[S:28][C:29]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[N:30]2)[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)=[O:15]>O.ClCCl.CC(C)=O>[OH:12][CH:13]([N:26]1[C@H:27]([SH:28])[C@H:31]([NH:30][C:29](=[O:8])[CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:32]1=[O:33])[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)=[O:15]

Participants

6

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 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 544549564-methoxybenzyl (2RS)-2-hydroxy-2-[(3R,4R)-4-mercapto-3-phenylacetamidoazetidin-2-on-1-yl]acetate

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Toluene-4-sulphonic acid (3.42 g, 17.98 mmol) in water (8 ml) was added to a solution of 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 (4.12 g, 10.0 mmol) in dichloromethane (20 ml) and acetone (20 ml). After stirring for 2.5 h at room temperature, the reaction mixture was diluted with dichloromethane, washed with water (×2), dried and concentrated in vacuo to yield crude 4-methoxybenzyl (2RS)-2-hydroxy-2-[(3R,4R)-4-mercapto-3-phenylacetamidoazetidin-2-on-1-yl]acetate as a colourless foam. The crude thiol was dissolved in acetone (50 ml) and treated with a solution of 2-bromoacetyl-5-methyltetrahydrofuran (1.67 g, 8.1 mmol) in acetone (5 ml). After 10 min., potassium carbonate (687 mg, 5.0 mmol) was added, and the mixture stirred for a further 30 min. The reaction mixture was diluted with ethyl acetate, washed successively with water (×2) and brine, dried and concentrated. The residue was purified by chromatography on silica gel eluting with 50, 70 and 80% ethyl acetate in hexane to yield the title compound as a colourless foam (2.68 g, 60%); νmax (CH2Cl2) 3412, 1781, 1744, 1685 and 1515 cm-1. [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (579)].

Workup

  1. washwashed with water (×2)
  2. customdried
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-05b44732c0d149cbab2db95c24a61c6e
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

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