Sodium Carbonate → Tert-butyl 4-{2-(2,6-diethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidin-4-yl}piperazine-1-carboxylate

HRID 1091940Notes

Reaction equation

HRID 1091940 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([CH2:20][O:21][C:22]3[CH:27]=[C:26]([CH:28]([CH3:30])[CH3:29])[CH:25]=[CH:24][C:23]=3[CH3:31])=[C:18]([CH3:32])[N:17]=[C:16](Cl)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:34]([C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([CH2:42][CH3:43])[C:37]=1B(O)O)[CH3:35].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[CH2:34]([C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([CH2:42][CH3:43])[C:37]=1[C:16]1[N:15]=[C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[C:19]([CH2:20][O:21][C:22]2[CH:27]=[C:26]([CH:28]([CH3:30])[CH3:29])[CH:25]=[CH:24][C:23]=2[CH3:31])=[C:18]([CH3:32])[N:17]=1)[CH3:35]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 18437832(2,6-Diethylphenyl)boronic acidHCID 575313954-[2-Chloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 11548705Tert-butyl 4-{2-(2,6-diethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-6-methylpyrimidin-4-yl}piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-[2-chloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (700 mg, 1.47 mmol), 2,6-diethylphenylboronic acid (394 mg, 2.21 mmol), 2 M aqueous sodium carbonate (2.21 mL, 4.42 mmol) and toluene (5 mL) is degassed with argon bubbling for 15 min. Pd(PPh3)4 (87 mg, 5 mol %) is added and the resulting yellow-colored mixture is heated at 90° C. under nitrogen with magnetic stirring for 40 h. The reaction mixture is partitioned between EtOAc (50 mL) and water (15 mL), the organic layer is separated, washed with water (15 mL), bring (15 mL), dried over sodium sulfate, filtered and evaporated at reduced pressure to obtain a yellow liquid. Chromatography on a 30 g silica gel cartridge (10-30% EtOAc/Hexanes) affords the title compound as a colorless oil (along with recovered 4-[2-chloro-5-(5-isopropyl-2-methyl-phenoxymethyl)-6-methyl-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester). LC/MS (Method 3), M+H=573.2, Rt=3.18 min.; 1H NMR (CDCl3) δ=7.26 (d, 1H), 7.12 (d, 3H), 6.83 (m, 2H), 4.99 (s, 2H), 3.51 (m, 4H), 2.90 (m, 6H), 2.55, (s, 3H), 2.42 (q, 4H) 2.24 (s, 3H), 1.28 (d, 6H), 1.10 (t, 6H).

Workup

  1. customis degassed with argon bubbling for 15 min
  2. additionPd(PPh3)4 (87 mg, 5 mol %) is added
  3. customThe reaction mixture is partitioned between EtOAc (50 mL) and water (15 mL)
  4. customthe organic layer is separated
  5. washwashed with water (15 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated at reduced pressure
  9. customto obtain a yellow liquid

Sources & evidence

ORD record
ord-044cb9987f7741dfb08fbce2c0bfcff3
Source dataset
uspto-grants-2012_03
Patent number
US08129395B2

Reaction notes

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