tert-Butyl piperazine-1-carboxylate → N-tert-Butyldimethylsilyl-4-(4-Boc-piperazinyl)-indole

HRID 2112442

Reaction equation

HRID 2112442 reaction equation
[Si:1]([N:8]1[C:16]2[C:11](=[C:12](Cl)[CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[N:18]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(O[Na])(C)(C)C.OP([O-])(O)=O.[K+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Si:1]([N:8]1[C:16]2[C:11](=[C:12]([N:21]3[CH2:20][CH2:19][N:18]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23][CH2:22]3)[CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 516951Monobasic potassium phosphateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 164270964-Chloro-N-(tert-butyldimethylsilyl)indoleHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 22015338N-tert-Butyldimethylsilyl-4-(4-Boc-piperazinyl)-indole

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

The compound was prepared according to Method 2 from N-tert-butyldimethylsilyl-4-chloroindole (100 g, 376 mmol, 1 equiv.), tert-butyl 1-piperazinecarboxylate (84 g, 451 mmol), Palladium(II)acetate (1.26 g., 5.62 mmol, 2%), 2-(dicyclohexylphosphino) biphenyl (3.95 g., 11.28 mmol, 4 mol %) tert-BuONa (50 g, 520 mmol, 1.4 equiv.) in toluene. The solution was cooled to room temperature and KH2PO4 (150 mL, 13% aqueous solution) was added and pH was adjusted (pH=8-9) followed by extraction with toluene (2×100 mL), dried (MgSO4) and evaporated. The residue was crystallized from heptane to yield 124.4 g (79.6%). 1H NMR (CDCl3)δ 7.20 (d, J=8.4 Hz, 1H), 7.13 (d, J=3.2 Hz, 1H), 7.06 (t, 1H), 6.60-6.57 (m, 2H), 3.65 (t, 4H), 3.16 (t, 4H), 1.48 (s, 9H), 0.91 (s, 9H), 0.58 (s, 6H); 13C NMR (CDCl3) δ 155.0; 145.5; 142.2; 129.9; 124.9; 122.0; 109.3; 107.2; 102.9; 79.8; 77.3; 51.5; 28.5; 26.4; 19.5; −3.8; MS (ESI) 416.4 (M+H).

Workup

  1. customThe compound was prepared
  2. extractionfollowed by extraction with toluene (2×100 mL)
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe residue was crystallized from heptane
  6. customto yield 124.4 g (79.6%)

Sources & evidence

ORD record
ord-76d52c6f324041a0bd93a40aa23506a4
Source dataset
uspto-grants-2009_04
Patent number
US07524839B2

Linked notes

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