(2-Methoxyethyl)(methyl)amine → {3-Chloro-2-fluoro-5-[(2-methoxy-ethyl)-methyl-amino]-benzyl}-carbamic acid tert-butyl ester

HRID 1527476Notes

Reaction equation

HRID 1527476 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[CH:14]=[C:13](Br)[CH:12]=[C:11]([Cl:16])[C:10]=1[F:17])([CH3:4])([CH3:3])[CH3:2].[CH3:19][O:20][CH2:21][CH2:22][NH:23][CH3:24].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([N:23]([CH2:22][CH2:21][O:20][CH3:19])[CH3:24])[CH:12]=[C:11]([Cl:16])[C:10]=1[F:17])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 300977(2-Methoxyethyl)(methyl)amineHCID 23676156Sodium t-butoxideHCID 68283623Carbamic acid, N-[(5-bromo-3-chloro-2-fluorophenyl)methyl]-, 1,1-dimethylethyl ester

Product 1

HCID 68284073{3-Chloro-2-fluoro-5-[(2-methoxy-ethyl)-methyl-amino]-benzyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
140 °C

Procedure

A suspension of (5-bromo-3-chloro-2-fluoro-benzyl)-carbamic acid tert-butyl ester (250 mg, 0.7 mmol), N-methoxyethyl-methylamine (99 mg, 1.1 mmol), sodium tert-butoxide (142 mg, 1.5 mmol) and di-μ-bromobis(tri-tert-butylphosphino)dipalladium (I) [CAS 185812-86-6] (29 mg, 0.04 mmol) in toluene (5 mL) was sealed in a microwave vial and heated for 30 min at 140° C. (Emrys Optimizer; personal chemistry). The reaction mixture was quenched by addition of saturated aqueous NaHCO3, extracted with EtOAc, dried (Na2SO4) and evaporated in vacuo. The crude product was purified by RP-preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min) to give the title compound after lyophilization. MS (LC/MS): 347.0 [M]+. tR (HPLC conditions c): 5.23 min.

Workup

  1. customwas sealed in a microwave vial
  2. customThe reaction mixture was quenched by addition of saturated aqueous NaHCO3
  3. extractionextracted with EtOAc
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. customThe crude product was purified by RP-preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min)

Sources & evidence

ORD record
ord-066b4a954f104ba1b24a8e6c4782f5a5
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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