Triethylamine → 5-Methanesulfonyloxymethyl-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester

HRID 1406799Notes

Reaction equation

HRID 1406799 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:20][OH:21])[CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:29][S:30](Cl)(=[O:32])=[O:31].C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O.[Cl-].[Na+].O>[CH2:1]([O:8][C:9]([N:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:20][O:21][S:30]([CH3:29])(=[O:32])=[O:31])[CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 516892Sodium BicarbonateHCID 579902105-Hydroxymethyl-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester

Product 1

HCID 579902125-Methanesulfonyloxymethyl-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 5-hydroxymethyl-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester (65.75 g, 0.232 mol) in THF (470 mL) and EtOAc (770 mL) was added Et3N (39 mL, 0.28 mol). The solution was cooled in an ice-bath and a solution of methanesulphonyl chloride (19 mL, 0.245 mol) dissolved in EtOAc (50 mL) was added (so that the internal temp <12° C.). After stirring for 2 h in the ice-bath further additions of methanesulphonyl chloride (1.9 mL and 0.95 mL) and Et3N (3.9 mL) were made (so that by tlc there was no remaining starting material after a further 1 h of stirring). NaHCO3 (550 mL) was added and the solution stirred for 20 mins then saturated brine (200 mL) was added and the phases were separated. The organic phase was dried (MgSO4) and evaporated with seeding to give a damp solid which was used in the next step without thorough drying.

Workup

  1. temperatureThe solution was cooled in an ice-bath
  2. additionwas added (so that the internal temp <12° C.)
  3. customafter a further 1 h
  4. stirringthe solution stirred for 20 mins
  5. customthe phases were separated
  6. dry with materialThe organic phase was dried (MgSO4)
  7. customevaporated
  8. customto give a damp solid which

Sources & evidence

ORD record
ord-af7eff53a1224a23a32b9da85b064652
Source dataset
uspto-grants-2014_12
Patent number
US08916552B2

Reaction notes

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