Sodium Carbonate → [2-(2-Chloropyrimidin-4-yl)-benzo[b]thiophen-6-ylmethyl]-carbamic acid tert-butyl ester

HRID 1986191

Reaction equation

HRID 1986191 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]2[CH:16]=[CH:15][S:14][C:13]=2[CH:17]=1)([CH3:4])([CH3:3])[CH3:2].C(OB(OC(C)C)OC(C)C)(C)C.C(NC(C)C)(C)C.[Li].[Cl:40][C:41]1[N:46]=[C:45](Cl)[CH:44]=[CH:43][N:42]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]2[CH:16]=[C:15]([C:43]3[CH:44]=[CH:45][N:46]=[C:41]([Cl:40])[N:42]=3)[S:14][C:13]=2[CH:17]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

10

Reactant 5

HCID 10340Sodium CarbonateHCID 21531Triisopropyl borateHCID 775312,4-DichloropyrimidineHCID 45051747Lithium diisopropylamineHCID 68856189HCID 68856189, compound

Product 1

HCID 86625348[2-(2-Chloropyrimidin-4-yl)-benzo[b]thiophen-6-ylmethyl]-carbamic acid tert-butyl esterYield 28.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Benzo[b]thiophen-6-ylmethyl-carbamic acid tert-butyl ester (3.6 g, 13.8 mmol) is dissolved in THF (100 mL) and cooled to −78° C. Triisopropylborate (8.5 mL) is added, followed by lithium diisopropylamine solution (27 mL of 2.0 M solution), and the reaction is allowed to slowly warm to room temperature over two hours. The reaction is stirred at room temperature for two hours at which time 2,4-dichloropyrimidine (4.59 g, 30.8 mmol), 1,1′-bis(diphenylphosphino)ferrocene (388 mg, 0.700 mmol), palladium (II) acetate (164 mg, 0.730 mmol) and sodium carbonate (28 mL of 2.0 N solution) are added. The reaction is heated for 20 hours at 70° C. After the reaction solution is cooled to 25° C., water (100 mL) is added. The mixture is extracted with dichloromethane and the extracts are evaporated. The resulting solid is subjected to chromatography on silica gel, eluting with EtOAc/hexanes 5-50%, to give the title compound (1.47 g, 28% yield). ES+(m/z) 376 (35Cl) and 378 (37Cl) [M+H].

Workup

  1. temperatureto slowly warm to room temperature over two hours
  2. additionare added
  3. temperatureThe reaction is heated for 20 hours at 70° C
  4. temperatureAfter the reaction solution is cooled to 25° C.
  5. extractionThe mixture is extracted with dichloromethane
  6. customthe extracts are evaporated
  7. washeluting with EtOAc/hexanes 5-50%

Sources & evidence

ORD record
ord-e08a8a8ea1ef49318e0c9e06e6350068
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Linked notes

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