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

HRID 864197Notes

Reaction equation

HRID 864197 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-17cda84d58cf41ccb846461e7cea3256
Source dataset
uspto-grants-1996_10
Patent number
US05561128

Reaction notes

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