Potassium Carbonate → 4-Methoxybenzyl (2RS)-2-hydroxy-2-[(3R,4R)-4-(5-methyltetrahydrofuran-2-ylcarbonylmethylthio)-3-phenylacetamidoazetidin-2-on-1-yl]acetate

HRID 376601Notes

Reaction equation

HRID 376601 reaction equation
[OH:1][CH:2]([N:15]1[C@H:18]([SH:19])[C@H:17]([NH:20][C:21](=[O:29])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:16]1=[O:30])[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].Br[CH2:32][C:33]([CH:35]1[CH2:39][CH2:38][CH:37]([CH3:40])[O:36]1)=[O:34].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.C(OCC)(=O)C>[OH:1][CH:2]([N:15]1[C@H:18]([S:19][CH2:32][C:33]([CH:35]2[CH2:39][CH2:38][CH:37]([CH3:40])[O:36]2)=[O:34])[C@H:17]([NH:20][C:21](=[O:29])[CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:16]1=[O:30])[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

6

Reactant 3

HCID 11430Potassium CarbonateHCID 187800882-Bromo-1-(5-methyloxolan-2-yl)ethan-1-oneHCID 544549564-methoxybenzyl (2RS)-2-hydroxy-2-[(3R,4R)-4-mercapto-3-phenylacetamidoazetidin-2-on-1-yl]acetate

Product 1

HCID 1317216324-Methoxybenzyl (2RS)-2-hydroxy-2-[(3R,4R)-4-(5-methyltetrahydrofuran-2-ylcarbonylmethylthio)-3-phenylacetamidoazetidin-2-on-1-yl]acetateYield 60%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Toluene-4-sulphonic acid (3.42g, 17.98mmol) in water (8ml) 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 (4.12g, 10.0mmol) in dichloromethane (20ml) and acetone (20ml). After stirring for 2.5h at room temperature, the reaction mixture was diluted with dichloromethane, washed with water (x2), 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 (50ml) and treated with a solution of 2-bromoacetyl-5-methyltetrahydrofuran (1.67g, 8.1mmol) in acetone (5ml). After 10 min., potassium carbonate (687mg, 5.0mmol) was added, and the mixture stirred for a further 30 min. The reaction mixture was diluted with ethyl acetate, washed successively with water (x2) 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 (2.68g, 60%); vmax (CH2Cl2) 3412, 1781, 1744, 1685 and 1515cm-1. (Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (579)].

Workup

  1. washwashed successively with water (x2) and brine
  2. customdried
  3. concentrationconcentrated
  4. customThe residue was purified by chromatography on silica gel eluting with 50, 70 and 80% ethyl acetate in hexane

Sources & evidence

ORD record
ord-e87eae784a1e410abd64076f7c5e0f1c
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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