Acetic Acid → tert-butyl 4-[(4-cyano-2,3-dihydro-1H-inden-1-yl)methyl]piperazine-1-carboxylate

HRID 1519521Notes

Reaction equation

HRID 1519521 reaction equation
[CH:1]([CH:3]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([C:12]#[N:13])[C:6]=2[CH2:5][CH2:4]1)=O.[N:14]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[C:12]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[CH2:5][CH2:4][CH:3]2[CH2:1][N:17]1[CH2:16][CH2:15][N:14]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18]1)#[N:13]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 595686981-formyl-2,3-dihydro-1H-indene-4-carbonitrile

Product 1

HCID 86694450tert-butyl 4-[(4-cyano-2,3-dihydro-1H-inden-1-yl)methyl]piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-Formyl-2,3-dihydro-1H-indene-4-carbonitrile (0.22 g, 1.3 mmol) was dissolved in MeOH (8 mL) and treated with tert-butyl piperazine-1-carboxylate (0.35 g, 1.9 mmol) followed by treatment of sodium cyanoborohydride (0.40 g, 6.43 mmol) and few drops of Acetic acid. The resulting mixture was then stirred at room temperature overnight. LC indicated completion of the reaction. The reaction mixture was concentrated in vacuo, treated with EtOAc and washed with saturated NaHCO3, dried with Na2SO4, filtered and loaded into MPLC for separation over silica gel. with 10% MeOH in DCM to afford tert-butyl 4-[(4-cyano-2,3-dihydro-1H-inden-1-yl)methyl]piperazine-1-carboxylate. This material was further treated with TFA to remove the Boc group. Removal of volatiles gave rise to 1-(piperazin-1-ylmethyl)indane-4-carbonitrile, which was used as the crude. LC-MS (IE, m/z): 242 (M+1)+.

Workup

  1. customcompletion of the reaction
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additiontreated with EtOAc
  4. washwashed with saturated NaHCO3
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. customloaded into MPLC for separation over silica gel

Sources & evidence

ORD record
ord-4e9d40430fb14692a2c6f5db31129db8
Source dataset
uspto-grants-2015_07
Patent number
US09073882B2

Reaction notes

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