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Trichloroacetonitrile → (+/-)-1-(3-Bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethyl 2,2,2-trichloroacetimidate

HRID 913876
Notes
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Reaction equation

HRID 913876 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[C:6]([CH:12]([OH:14])[CH3:13])[CH:7]=[C:8]([Cl:11])[CH:9]=2)[N:4]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:3]=1.N12CCCN=C1CCCCC2.[Cl:34][C:35]([Cl:39])([Cl:38])[C:36]#[N:37]>C(Cl)Cl>[Cl:34][C:35]([Cl:39])([Cl:38])[C:36](=[NH:37])[O:14][CH:12]([C:6]1[CH:7]=[C:8]([Cl:11])[CH:9]=[C:10]2[C:5]=1[N:4]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:21])([CH3:20])[CH3:22])[N:3]=[C:2]2[Br:1])[CH3:13]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 11011TrichloroacetonitrileHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 57546143HCID 57546143, compound

Product 1

HCID 57546223(+/-)-1-(3-Bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethyl 2,2,2-trichloroacetimidate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(±)-1-(3-Bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)ethanol (1.29 g, 3.18 mmol) was dissolved in methylene chloride (10 mL), cooled to 0° C. and treated with 1,8-diazabicyclo(5.4.0)undec-7-ene (96 μL, 0.64 mmol). The reaction was stirred for 10 min and treated with trichloroacetonitrile (3.19 mL, 31.8 mmol) dropwise over 10 min. The ice bath was removed and the reaction stirred at room temperature for 1 h and concentrated. Flash chromatography on silica gel (5% ethyl acetate/hexanes) gave 1.69 g (77%) as an oil. 1H-NMR (CDCl3, 300 MHz) δ 8.27 (s, 1H), 7.59 (d, J=1.8 Hz, 1H), 7.53 (d, J=1.8 Hz, 1H), 6.58 (q, J=6.6 Hz, 1H), 6.19 (qAB, JAB=11.4 Hz, 2H), 3.50-3.56 (m, 2H), 1.74 (m, 3H), 0.80-0.84 (m, 2H), 0.06 (s, 9H).

Workup

  1. customThe ice bath was removed
  2. stirringthe reaction stirred at room temperature for 1 h
  3. concentrationconcentrated
  4. customFlash chromatography on silica gel (5% ethyl acetate/hexanes) gave 1.69 g (77%) as an oil

Sources & evidence

ORD record
ord-c5a6012a545d4b649faea66e0ca3d94d
Source dataset
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08026257B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes