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

HRID 362273Notes

Reaction equation

HRID 362273 reaction equation
[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]

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-883c845d9ead478aa65ac82f3de80cd1
Source dataset
uspto-grants-1999_02
Patent number
US05869496

Reaction notes

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