tert-Butyl piperazine-1-carboxylate → 3-[4-(tert-Butoxycarbonyl)piperazin-1-yl]-5-(pentafluoro-lambda6-sulphanyl)benzoic acid

HRID 1055642Notes

Reaction equation

HRID 1055642 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([S:11]([F:16])([F:15])([F:14])([F:13])[F:12])[CH:10]=1)[C:5]([OH:7])=[O:6].[N:17]1([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:26]([O:25][C:23]([N:17]1[CH2:22][CH2:21][N:20]([C:2]2[CH:3]=[C:4]([CH:8]=[C:9]([S:11]([F:16])([F:15])([F:14])([F:13])[F:12])[CH:10]=2)[C:5]([OH:7])=[O:6])[CH2:19][CH2:18]1)=[O:24])([CH3:29])([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 23676156Sodium t-butoxideHCID 58137421HCID 58137421, compound

Product 1

HCID 896995763-[4-(tert-Butoxycarbonyl)piperazin-1-yl]-5-(pentafluoro-lambda6-sulphanyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

3.0 g (9.2 mmol) of the compound of Example 15A and 2.05 g (11.0 mmol) of tert-butyl piperazine-1-carboxylate were initially charged in 80 ml of toluene and the mixture was degassed with argon. 135 mg (0.18 mmol) of [2-(2-aminoethyl)phenyl](chloro)palladiumdicyclohexyl-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphane/tert-butyl methyl ether adduct, 87.5 mg (0.18 mmol) of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphane and 2.1 g (22.0 mmol) of sodium tert-butoxide were added successively to this solution. The mixture was stirred at 110° C. for 3 h. After this, another 67.8 mg (0.09 mmol) of [2-(2-aminoethyl)phenyl](chloro)palladiumdicyclohexyl-(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphane/tert-butyl methyl ether adduct and 43.8 mg (0.09 mmol) of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphane were added and the mixture was stirred at 110° C. for a further 3 h. The hot mixture was then filtered through kieselguhr, and the mother liquor was concentrated on a rotary evaporator. The residue was suspended in 50 ml of pH 7 buffer solution and the precipitated solid was filtered off. The filter cake was washed with water and dried under reduced pressure. The residue was triturated with 20 ml of methylene chloride, the suspension was filtered again and the filter cake was once more dried under reduced pressure. This gave 2.98 g (72% of theory) of the title compound.

Workup

  1. customthe mixture was degassed with argon
  2. stirringthe mixture was stirred at 110° C. for a further 3 h
  3. filtrationThe hot mixture was then filtered through kieselguhr
  4. concentrationthe mother liquor was concentrated on a rotary evaporator
  5. filtrationthe precipitated solid was filtered off
  6. washThe filter cake was washed with water
  7. customdried under reduced pressure
  8. customThe residue was triturated with 20 ml of methylene chloride
  9. filtrationthe suspension was filtered again
  10. customthe filter cake was once more dried under reduced pressure

Sources & evidence

ORD record
ord-f2669bc960df45288c6b2a66731dced5
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

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