Dimethyl Sulfate → HCID 131719643, compound

HRID 1900436Notes

Reaction equation

HRID 1900436 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16]N4C(O)C5C(=CC=CC=5)C4=O)[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[CH3:30][C:31]([CH3:34])([O-])[CH3:32].[K+].S([O:41][CH3:42])(OC)(=O)=O.[CH2:43]1[CH2:47][O:46][CH2:45][CH2:44]1>>[F:1][C:2]1[CH:29]=[CH:28][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:15][C@@H:16]([O:41][CH3:42])[CH2:34][C:31]4[CH:32]=[CH:44][CH:43]=[C:47]([O:46][CH3:45])[CH:30]=4)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

5

Reactant 4

HCID 6497Dimethyl SulfateHCID 8028TetrahydrofuranHCID 184672142-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl-2,3-dihydro-3-hydroxy-1H-isoindol-1-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 131719643HCID 131719643, compoundYield 46%

Procedure

To a solution of 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-2,3-dihydro-3-hydroxy-1H-isoindol-1-one (3.3 g, 11.3 mmol) in dry THF (120 ml) was added potassium tert-butoxide (1.9 g, 16.9 mmol) followed by dimethyl sulfate (1.2 ml, 11.9 mmol) at room temperature, under nitrogen. The reaction mixture was stirred for 21 hours at which time it was filtered through a pad of Celite and the solids washed with EtOAc. The combined filtrates were concentrated to give the crude product. Purification via flash column chromatography (silica gel, 0-20% acetone/DCM) afforded 1.6 g (46%) of the desired product as a solid, m.p. =40°-42° C.

Workup

  1. filtrationwas filtered through a pad of Celite
  2. washthe solids washed with EtOAc
  3. concentrationThe combined filtrates were concentrated
  4. customto give the crude product
  5. customPurification via flash column chromatography (silica gel, 0-20% acetone/DCM)

Sources & evidence

ORD record
ord-62bf989f0890433e88aa4377c100025a
Source dataset
uspto-grants-1996_11
Patent number
US05574032

Reaction notes

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