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

HRID 1527476
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HRID 1527476 반응식
[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]
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참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
140 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-066b4a954f104ba1b24a8e6c4782f5a5
출처 데이터셋
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09085555B2

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