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ethyl 7-(bromomethyl)-6-chloro-2-(trifluoromethyl)-2H-chromene-3-carboxylate → ethyl 6-chloro-7-[(5-methylpyridin-2-yl)methyl]-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 855046
Notes
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Reaction equation

HRID 855046 reaction equation
Br[Mg][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][N:4]=1.Br[CH2:11][C:12]1[CH:21]=[C:20]2[C:15]([CH:16]=[C:17]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:18]([C:22]([F:25])([F:24])[F:23])[O:19]2)=[CH:14][C:13]=1[Cl:31]>[Cl-].[Cl-].[Zn+2].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[Cl:31][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:12]=1[CH2:11][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][N:4]=1)[O:19][CH:18]([C:22]([F:25])([F:24])[F:23])[C:17]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:16]2
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 2

HCID 69517129ethyl 7-(bromomethyl)-6-chloro-2-(trifluoromethyl)-2H-chromene-3-carboxylateHCID 178426145HCID 178426145, compound

Product 1

HCID 69517746ethyl 6-chloro-7-[(5-methylpyridin-2-yl)methyl]-2-(trifluoromethyl)-2H-chromene-3-carboxylateYield 15%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalyst
HCID 178418476
HCID 178418476, compound
Catalyst
HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

The bromo (5-methylpyridin-2-yl)magnesium (10.4 mL, 2.6 mmole) was diluted by 5 mL THF under nitrogen and the solution was cooled to −78° C. ZnCl2 (340 mg, 2.5 mmole) was added to above solution and the mixture was stirred for 0.5 hr. The ethyl 7-(bromomethyl)-6-chloro-2-(trifluoromethyl)-2H-chromene-3-carboxylate from Example 16, Step 3 (01597/1 PR) (1.0 g, 2.5 mmol) was added to above mixture and followed by PdCl2(PPh3)2 (18 mg, 0.025 mmole). The mixture was warmed to room temperature and heated to 50° C. for 3 hr. LCMS indicated that the product was formed around 15%. The solid was filtered off and the filtrate was concentrated to give a crude mixture, which was purified by RPHPLC eluted with 10 to 95% ACN in water with 0.05% TFA to afford 150 mg the desired product as a brown oil (yield 15%), which had suitable purity to use without further purification.

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. temperatureheated to 50° C. for 3 hr
  3. customwas formed around 15%
  4. filtrationThe solid was filtered off
  5. concentrationthe filtrate was concentrated
  6. customto give a crude mixture, which
  7. customwas purified by RPHPLC
  8. washeluted with 10 to 95% ACN in water with 0.05% TFA

Sources & evidence

ORD record
ord-a2e5c6a152c44be2b5623e658da644b7
Source dataset
uspto-grants-2007_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07259266B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes