Tetrahydrofuran → (S)-3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-methylpropylmethyl carbamate

HRID 975419Notes

Reaction equation

HRID 975419 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.C[N:31]=[C:32]=[O:33].[C:34]([O-])([O-])=O.[K+].[K+].C1C[O:43][CH2:42][CH2:41]1>>[C:32](=[O:33])([O:43][CH2:42][CH2:41][C@H:16]([CH3:34])[CH2:15][N:12]1[CH2:11][CH2:10][CH:9]([C:6]2[C:5]3[CH:28]=[CH:29][C:2]([F:1])=[CH:3][C:4]=3[O:8][N:7]=2)[CH2:14][CH2:13]1)[NH2:31]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 12228Methyl IsocyanateHCID 184672142-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl-2,3-dihydro-3-hydroxy-1H-isoindol-1-one

Product 1

HCID 53784931(S)-3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-methylpropylmethyl carbamateYield 73%

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 (3.1 g, 10.6 mmol) in dry THF (120 ml) was added methyl isocyanate (0.66 ml, 11.1 mmol) followed by milled K2CO3 (2.2 g, 15.9 mmol) at room temperature, under nitrogen. The reaction mixture was stirred for 3 days 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 which was purified via flash column chromatography (silica gel, 2% Et3N/EtOAc). The product containing fractions were concentrated to give 2.7 g (73%) of the desired product as an oil which solidified on standing. Recrystallization from EtOAc/pet.ether gave the product as a solid, m.p.=72°-74° 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 which
  5. customwas purified via flash column chromatography (silica gel, 2% Et3N/EtOAc)
  6. additionThe product containing fractions
  7. concentrationwere concentrated

Sources & evidence

ORD record
ord-bfe7ea0a46a34b99a603181a0c982051
Source dataset
uspto-grants-1997_03
Patent number
US05607945

Reaction notes

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