Potassium Carbonate → [5-(4-Benzyloxy-3-fluoro-phenyl)-6-chloro-1H-benzimidazol-2-ylsulfanyl]-acetic acid tert-butyl ester

HRID 1045105Notes

Reaction equation

HRID 1045105 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][C:10]=1[F:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19]([O:23][C:24](=[O:38])[CH2:25][S:26][C:27]1[NH:31][C:30]2[CH:32]=[C:33]([Cl:37])[C:34](I)=[CH:35][C:29]=2[N:28]=1)([CH3:22])([CH3:21])[CH3:20].C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.O.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>[C:19]([O:23][C:24](=[O:38])[CH2:25][S:26][C:27]1[NH:31][C:30]2[CH:32]=[C:33]([Cl:37])[C:34]([C:12]3[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[C:10]([F:18])[CH:11]=3)=[CH:35][C:29]=2[N:28]=1)([CH3:22])([CH3:20])[CH3:21]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 58387110Tert-butyl 2-(6-chloro-5-iodo-1H-benzo[d]imidazol-2-ylthio)acetate2×

Product 1

HCID 58387185[5-(4-Benzyloxy-3-fluoro-phenyl)-6-chloro-1H-benzimidazol-2-ylsulfanyl]-acetic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A 4 mL vial with a septum cap and a stirring bar was charged with 4-benzyloxy-3-fluoro-phenylboronic acid (14.8 mg, 0.060 mmol) and Pd(PPh3)4 (5.8 mg, 5 mol %) and was purged briefly with N2. A solution of (6-chloro-5-iodo-1H-benzoimidazol-2-ylsulfanyl)-acetic acid tert-butyl ester (Intermediate 4, 21.4 mg, 0.050 mmol) in toluene (200 uL) was added to the vial, followed by a solution K2CO3 (21.4 mg, 0.050 mmol) in water (100 uL). The resulting mixture was stirred at 80° C. for 14 h. The mixture was allowed to cool down to rt, and was partitioned with EtOAc (1 mL) and 10% aqueous AcOH (1 mL). The organic layer was separated evaporated to dryness in vacuo. LR-MS (API-ES) of the residue confirmed the presence of the title compound: calculated for C26H24ClFN2O3S 498.1, observed m/e 499.0 (M+H)+ (Rt 3.54 min). The crude product was used in the next step without further purification.

Workup

  1. customA 4 mL vial with a septum cap
  2. customwas purged briefly with N2
  3. temperatureto cool down to rt
  4. customwas partitioned with EtOAc (1 mL) and 10% aqueous AcOH (1 mL)
  5. customThe organic layer was separated
  6. customevaporated to dryness in vacuo
  7. customThe crude product was used in the next step without further purification

Sources & evidence

ORD record
ord-71ab1517df124420bf568b5d47a7daa8
Source dataset
uspto-grants-2013_10
Patent number
US08563746B2

Reaction notes

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