Ethyl 2-(tributylstannyl)acetate → Ethyl 2-(3-(benzyloxy)naphthalen-1-yl)acetate

HRID 900149Notes

Reaction equation

HRID 900149 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11](Br)[C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:20]([O:22][C:23](=[O:38])[CH2:24][Sn](CCCC)(CCCC)CCCC)[CH3:21]>CN(C=O)C.CCOC(C)=O.[Br-].[Zn+2].[Br-]>[CH2:20]([O:22][C:23](=[O:38])[CH2:24][C:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:18]=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:10]=1)[CH3:21]

Participants

6

Reactant 2

HCID 10894129Ethyl 2-(tributylstannyl)acetateHCID 211145093-(Benzyloxy)-1-bromonaphthalene

Product 1

HCID 44479435Ethyl 2-(3-(benzyloxy)naphthalen-1-yl)acetate

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

3-Benzyloxy-1-bromo-naphthalene (5.64 g, 18.01 mmol) is dissolved under an atmosphere of argon in dry DMF (100 ml). Tributylstannanyl-acetic acid ethyl ester (7.47 g, 19.81 mmol) is added, as well as [bis(tri-ortho-tolyl-phosphine)]palladium (II) dichloride (2.83 g, 3.60 mmol) and zinc(II) bromide (5.27 g, 23.41 mmol). The reaction mixture is heated to 80° C. for 3 h. The reaction mixture is diluted with EtOAc and washed twice with diluted brine (back extracted). The combined organic layers are dried over Na2SO4, the solvent is removed, and the residue is purified by FCC (hexane/EtOAc 100:0 to 97.5:2.5 to 95:5 to 90:10). The resulting oil, still containing tin residues, is stirred in a 1:1 mixture of EtOAc/1N NaOH (200 ml) for 1 h. The mixture is extracted twice with EtOAc. The combined organic layers are washed twice with H2O (back extracted), dried over Na2SO4 and concentrated. The residue is purified by FCC (hexane/EtOAc 100:0 to 97:3 to 95:5 to 93:7 to 92:8 to 90:10) to yield the title compound. 1H NMR (DMSO, 400 MHz) δ 1.18 (t, J=7.2 Hz, 3H), 4.10 (q, J=7.2 Hz, 2H), 4.11 (s, 2H), 5.25 (s, 2H), 7.21 (d, J=3.0 Hz, 1H), 7.41 (m, 8H), 7.53 (d, J=6.6 Hz, 1H), 7.84 (dd, J=7.2 Hz, 1H); ES-MS: 320 [M+H]+.

Workup

  1. washwashed twice with diluted brine (back extracted)
  2. dry with materialThe combined organic layers are dried over Na2SO4
  3. customthe solvent is removed
  4. customthe residue is purified by FCC (hexane/EtOAc 100:0 to 97.5:2.5 to 95:5 to 90:10)
  5. extractionThe mixture is extracted twice with EtOAc
  6. washThe combined organic layers are washed twice with H2O (back extracted)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue is purified by FCC (hexane/EtOAc 100:0 to 97:3 to 95:5 to 93:7 to 92:8 to 90:10)

Sources & evidence

ORD record
ord-c3a78a795fe043a886bdcfb63f4d5869
Source dataset
uspto-grants-2008_04
Patent number
US07358253B2

Reaction notes

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