Hydrochloric Acid → Methanesulfonic acid 2-[3-benzyloxy-5-fluoro-4-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-benzyl]-5-methylphenyl ester

HRID 889249Notes

Reaction equation

HRID 889249 reaction equation
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([OH:17])[C:3]=1[N:18]1[S:22](=[O:24])(=[O:23])[NH:21][C:20](=[O:25])[CH2:19]1.Br[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][C:29]=1[O:35][S:36]([CH3:39])(=[O:38])=[O:37].C([O-])([O-])=O.[Na+].[Na+].Cl>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:27]([O:17][C:4]1[CH:5]=[C:6]([CH:7]=[C:2]([F:1])[C:3]=1[N:18]1[CH2:19][C:20](=[O:25])[NH:21][S:22]1(=[O:23])=[O:24])[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][C:29]=1[O:35][S:36]([CH3:39])(=[O:38])=[O:37])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 684295315-[2-Fluoro-6-hydroxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-1,1-dioxo-1,2,5-thiadiazolidin-3-oneHCID 86638983Methanesulfonic acid 2-bromomethyl-5-methylphenyl ester

Product 1

HCID 86638984Methanesulfonic acid 2-[3-benzyloxy-5-fluoro-4-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-benzyl]-5-methylphenyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 5-[2-fluoro-6-hydroxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one (150 mg, 0.325 mmol) and Pd(PPh3)4 (38 mg, 0.0325 mmol) in DME (2 mL) is heated at 60° C. under argon for 1 h. Then methanesulfonic acid 2-bromomethyl-5-methylphenyl ester (181 mg, 0.65 mmol) and Na2CO3 (2N solution, 0.81 mL) is added. The mixture is heated at 120° C. in a microwave for 20 min. 1N HCl is added and the reaction mixture is extracted with EtOAc. The organic layer is washed with brine, dried over MgSO4 and filtered. The filtrate is concentrated to give the title compound and it is used directly in the next step: MS (M−H)−=533.

Workup

  1. temperatureThe mixture is heated at 120° C. in a microwave for 20 min
  2. extractionthe reaction mixture is extracted with EtOAc
  3. washThe organic layer is washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationThe filtrate is concentrated

Sources & evidence

ORD record
ord-45a47038d13d456f9e5fd776cedc860e
Source dataset
uspto-grants-2012_08
Patent number
US08252820B2

Reaction notes

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