Potassium Carbonate → 4-[2-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-pyrimidin-4-yl]piperazine-1-carboxylic acid tert-butyl ester

HRID 2175062Notes

Reaction equation

HRID 2175062 reaction equation
C1(C)C=CC=CC=1.C(O)C.C(=O)([O-])[O-].[K+].[K+].[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:35]=[CH:34][N:33]=[C:32](Cl)[N:31]=2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].CC1(C)C(C)(C)OB([C:45]2[CH:54]=[CH:53][C:52]3[C:51]([CH3:56])([CH3:55])[CH2:50][CH2:49][C:48]([CH3:58])([CH3:57])[C:47]=3[CH:46]=2)O1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.ClCCl.O>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:35]=[CH:34][N:33]=[C:32]([C:54]3[CH:45]=[CH:46][C:47]4[C:48]([CH3:58])([CH3:57])[CH2:49][CH2:50][C:51]([CH3:56])([CH3:55])[C:52]=4[CH:53]=3)[N:31]=2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 11197306Tert-butyl 4-(2-chloropyrimidin-4-yl)piperazine-1-carboxylateHCID 112439294,4,5,5-Tetramethyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1,3,2-dioxaborolaneHCID 21863594Toluene ethanol

Product 1

HCID 672484304-[2-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-pyrimidin-4-yl]piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

2.6 ml of toluene/ethanol (4:1) and 335 μl of 2N potassium carbonate solution are added to 100 mg (0.33 mmol) of 4-(2-chloropyrimidin-4-yl)piperazine-1-carboxylic acid tert-butyl ester (preparation analogous to US 2005/176722) and 147 mg (0.47 mmol) of 4,4,5,5-tetramethyl-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1,3,2-dioxaborolane. The reaction mixture is degassed a number of times, 16 mg (0.01 mmol) of tetrakis(triphenylphosphine)palladium(0) are added under nitrogen atmosphere, the mixture is treated in an ultrasound bath for 10 min and subsequently irradiated in the microwave at 140° C. for 10 min. Water and dichloromethane are added to the reaction mixture. The organic phase is separated off, and the aqueous phase is extracted three times with ethyl acetate. The combined organic phases are dried over Na2SO4 and evaporated. The crude product is purified by means of flash chromatography on silica gel.

Workup

  1. additionare added under nitrogen atmosphere
  2. additionthe mixture is treated in an ultrasound bath for 10 min
  3. customsubsequently irradiated in the microwave at 140° C. for 10 min
  4. customThe organic phase is separated off
  5. extractionthe aqueous phase is extracted three times with ethyl acetate
  6. dry with materialThe combined organic phases are dried over Na2SO4
  7. customevaporated
  8. customThe crude product is purified by means of flash chromatography on silica gel

Sources & evidence

ORD record
ord-4ca1ad7065be40409a1e89e3704ad228
Source dataset
uspto-grants-2015_06
Patent number
US09062015B2

Reaction notes

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