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

HRID 267019

反応式

HRID 267019 の反応式
[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]

参加物

5

反応物 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

生成物 1

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

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-db93f3b5e99641cca00c0629c3931c53
出典データセット
uspto-grants-1997_07
特許番号
US05652241

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