Sodium cyanoborohydride → 1'-[3-(S)-(3,4-dichlorophenyl)-4-(t-butoxycarbonyl(methylamino))-butyl]-spiro(1H-indene-1,4'-piperidine)

HRID 362273ノート

反応式

HRID 362273 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]([CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH3:15])[CH2:10][CH:11]=O)[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[NH:24]1[CH2:29][CH2:28][C:27]2([C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:31]=[CH:30]2)[CH2:26][CH2:25]1.[BH3-]C#N.[Na+]>CO.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]([CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH3:15])[CH2:10][CH2:11][N:24]2[CH2:29][CH2:28][C:27]3([C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=[CH:30]3)[CH2:26][CH2:25]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

参加物

6

反応物 3

HCID 5003444Sodium cyanoborohydrideHCID 15433413tert-Butyl [(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl]methylcarbamateHCID 22509344Spiro[indene-1,4'-piperidine] hydrochloride

生成物 1

HCID 229423331'-[3-(S)-(3,4-dichlorophenyl)-4-(t-butoxycarbonyl(methylamino))-butyl]-spiro(1H-indene-1,4'-piperidine)収率 79%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 3.46 g (10 mmol) of 3-(S)-(3,4-dichlorophenyl)-4-(t-butoxycarbonyl-methylamino)butanal (Example 1) in 20 mL of methanol were added 3.11 g (14 mmol) of spiro(1H-indene-1,4'-piperidine) hydrochloride and 3 g of powdered 4 Å molecular sieves. After 15 min a solution of 2.52 g (40 mmol) of NaCNBH3 in 30 mL of THF was dropwise added. Some gas evolution was observed. After stirring the reaction overnight, the mixture was filtered through a pad of celite, the reaction flask and the pad were rinsed with methanol. The filtrate was concentrated to approximately 10 ml and the residue was partitioned between saturated NaHCO3 and Et2O:EtOAC. The organic layer was washed with water, brine and dried over NA2SO4. The filtrate was concentrated and the residue was chromatographed on a flash column using a gradient of 49:49:2 to 98:0:2 EtOAc:Hexane:triethylamine to furnish 4.05 g (79%) of the title compound as a foam.

後処理

  1. customthe reaction overnight
  2. filtrationthe mixture was filtered through a pad of celite
  3. washthe reaction flask and the pad were rinsed with methanol
  4. concentrationThe filtrate was concentrated to approximately 10 ml
  5. customthe residue was partitioned between saturated NaHCO3 and Et2O
  6. washThe organic layer was washed with water, brine
  7. customdried over NA2SO4
  8. concentrationThe filtrate was concentrated
  9. customthe residue was chromatographed on a flash column

出典と根拠

ORDレコード
ord-883c845d9ead478aa65ac82f3de80cd1
出典データセット
uspto-grants-1999_02
特許番号
US05869496

反応ノート

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