tert-Butyl piperazine-1-carboxylate → HCID 69420014, compound

HRID 1373635Notes

Reaction equation

HRID 1373635 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][O:6][CH2:7]2.[C:12]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].CC([O-])(C)C.[Na+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>[C:15]([O:14][C:12]([N:19]1[CH2:24][CH2:23][N:22]([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH2:4][CH2:5][O:6][CH2:7]3)[CH2:21][CH2:20]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 107986265-Bromo-3,4-dihydro-1H-2-benzopyranHCID 23676156Sodium t-butoxide

Product 1

HCID 69420014HCID 69420014, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 27342162-(Dicyclohexylphosphino)biphenylCatalyst

Procedure

A third intermediate compound, 1-Isochroman-5-yl-piperazine, was produced as follows: To a mixture of 5-bromo-isochroman (1 g, 4.69 mmol), 1-boc-piperazine (1.05 g, 5.6 mmol), 2-dicyclohexylphosphino biphenyl (0.066 g, 0.19 mmol), and Pd(OAc)2 (0.42 g, 0.19 mmol) in 10 mL of dry degassed C6H5CH3 was added NaOtBu (0.63 g, 6.6 mmol) at room temperature. The resulting mixture was stirred at 80–90° C. for 1 h, cooled and passed through a pad of celite and the filtrate was concentrated under vacuum. The residue was purified by chromatography (25–50% EtOAc/hexanes) to give 4-isochroman-5-yl-piperazine-1-carboxylic acid tert-butyl ester (0.89 g, 60%). MS (ES) m/z: 319.19 [M+1]. 1H NMR (400 MHz, CDCl3) δ 7.16 (t, J=7.8 Hz, 1H), 6.88 (d, J=7.8 Hz, 1H), 6.75 (d, J=7.8 Hz, 1H), 4.79 (s, 2H), 3.94 (t, J=5.9 Hz, 2H), 3.55 (br s, 4H), 2.86–2.80 (m, 4H), 1.49 (s, 9H).

Workup

  1. customof dry
  2. customdegassed C6H5CH3
  3. temperaturecooled
  4. concentrationthe filtrate was concentrated under vacuum
  5. customThe residue was purified by chromatography (25–50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6e0f2b885c484435b913704431c99200
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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