Dichloromethane → HCID 86296662, compound

HRID 1748402Notes

Reaction equation

HRID 1748402 reaction equation
Cl[C:2]1[C:11]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:10][C:9]2[C:4](=[CH:5][C:6]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)=[CH:7][CH:8]=2)[N:3]=1.ClCCl.CN(C)CCN(C)C.[BH4-].[Na+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.ClCCl>[Cl:26][C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=1)[CH2:19][O:18][C:6]1[CH:5]=[C:4]2[C:9]([CH:10]=[C:11]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:2]=[N:3]2)=[CH:8][CH:7]=1

Participants

10

Reactant 4

HCID 6344DichloromethaneHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 4311764Sodium borohydride2×HCID 90417116Ethyl 2-(2-chloro-7-((3-chlorobenzyl)oxy)quinolin-3-yl)acetate

Product 1

HCID 86296662HCID 86296662, compoundYield 55%

Reagents, catalysts & solvents 5

HCID 6344DichloromethaneCatalystHCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 2-(2-chloro-7-((3-chlorobenzyl)oxy)quinolin-3-yl)acetate (5 g, 12.8 mmol) in THF (50 mL) was degassed with nitrogen for 5 minutes and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1.36 g, 1.67 mmol) was added, followed by N1,N1,N2,N2-tetramethylethane-1,2-diamine (3.84 mL, 25.6 mmol) and sodium tetrahydroborate (969 mg, 25.6 mmol). The resulting solution was stirred at ambient temperature. After 4 h an additional portion of 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (50 mg, 0.06 mmol) and sodium tetrahydroborate (969 mg, 25.6 mmol) were added and stirred overnight. The reaction was quenched into sat. aqueous NH4Cl and extracted with EtOAc (3×30 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure to afford a brown oil. Purification (FCC, SiO2, 0-60%, EtOAc/hexanes) afforded the title compound as a colorless oil (2.5 g, 55%) that crystallized upon standing. 1H NMR (400 MHz, CDCl3) 8.76 (d, J=2.3 Hz, 1H), 8.02 (s, 1H), 7.71 (d, J=9.0 Hz, 1H), 7.52-7.43 (m, 2H), 7.32 (dd, J=6.5, 12.7 Hz, 4H), 5.19 (s, 2H), 4.18 (q, J=7.0 Hz, 2H), 3.77 (s, 2H), 1.26 (t, J=7.0 Hz, 3H). [M+H]=356.2.

Workup

  1. stirringstirred overnight
  2. customThe reaction was quenched into sat. aqueous NH4Cl
  3. extractionextracted with EtOAc (3×30 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customto afford a brown oil
  7. customPurification (FCC, SiO2, 0-60%, EtOAc/hexanes)

Sources & evidence

ORD record
ord-5c1ae26924c44b4580567311fd90e645
Source dataset
uspto-grants-2015_10
Patent number
US09150572B2

Reaction notes

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