Tributylphosphine → (6-(4-Bromo-7-fluoroindan-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetic acid methyl ester

HRID 2170930Notes

Reaction equation

HRID 2170930 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][CH:6]2[OH:12].[CH3:13][O:14][C:15](=[O:27])[CH2:16][CH:17]1[C:21]2[CH:22]=[CH:23][C:24](O)=[CH:25][C:20]=2[O:19][CH2:18]1.C(P(CCCC)CCCC)CCC.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[CH3:13][O:14][C:15](=[O:27])[CH2:16][CH:17]1[C:21]2[CH:22]=[CH:23][C:24]([O:12][CH:6]3[C:7]4[C:3](=[C:2]([Br:1])[CH:10]=[CH:9][C:8]=4[F:11])[CH2:4][CH2:5]3)=[CH:25][C:20]=2[O:19][CH2:18]1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 57345855Methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetateHCID 896215154-bromo-7-fluoro-2,3-dihydro-1H-inden-1-ol2×

Product 1

HCID 117965866(6-(4-Bromo-7-fluoroindan-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Reaction under argon atmosphere: to a solution of 15.3 g (66.3 mmol) of 4-bromo-7-fluoroindan-1-ol (product of step 1) and 11.0 g (53.0 mmol) of (6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetic acid methyl ester in 60.0 ml DCM are added 29.7 ml (116 mmol) of tributylphosphine. 24.4 ml (116 mmol) of diisopropylazodicarboxylate are added dropwise and under cooling in an ice/EtOH bath at 5° C.-15° C. over 20 min. It is stirred at r.t. for 1 h. The solvent is evaporated and the residue is chromatographed on silica gel (PE/EtOAc=100/0→95/5) to give the title compound. Yield: 16.9 g; LC (method 4): tR=4.84 min; Mass spectrum (ESI+): m/z=421 [M+H]+.

Workup

  1. customReaction under argon atmosphere
  2. temperatureunder cooling in an ice/EtOH bath at 5° C.-15° C. over 20 min
  3. customThe solvent is evaporated
  4. customthe residue is chromatographed on silica gel (PE/EtOAc=100/0→95/5)

Sources & evidence

ORD record
ord-07645c893aae4ef589da11f2890ce57d
Source dataset
uspto-grants-2015_06
Patent number
US09051289B2

Reaction notes

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