Benzyl Bromide → 4-Benzyloxy-2-hydroxymethyl-2,3-dihydro-benzofuran-6-carboxylic acid tert-butyl ester

HRID 1643673Notes

Reaction equation

HRID 1643673 reaction equation
[CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[C:15]([O:19][C:20]([C:22]1[CH:32]=[C:31]([OH:33])[C:25]2[CH2:26][CH:27]([CH2:29][OH:30])[O:28][C:24]=2[CH:23]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>CN(C=O)C>[C:15]([O:19][C:20]([C:22]1[CH:32]=[C:31]([O:33][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:25]2[CH2:26][CH:27]([CH2:29][OH:30])[O:28][C:24]=2[CH:23]=1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 25067321tert-Butyl 4-hydroxy-2-(hydroxymethyl)-2,3-dihydrobenzofuran-6-carboxylate

Product 1

HCID 595599544-Benzyloxy-2-hydroxymethyl-2,3-dihydro-benzofuran-6-carboxylic acid tert-butyl esterYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Benzyl bromide (1.8 mL, 15.2 mmol) and Cs2CO3 (4.89 g, 15.0 mmol) were added to a solution of 4-hydroxy-2-hydroxymethyl-2,3-dihydro-benzofuran-6-carboxylic acid tert-butyl ester (200f) (4.0 g, 15.0 mmol) in DMF (10 mL). The reaction mixture was stirred at room temperature overnight. The mixture was quenched with H2O (60 mL) and extracted EtOAc (2×60 mL). The organic layers were washed with H2O (2×100 mL), dried over MgSO4 and concentrated. The residue was purified by flash column chromatograph eluting with 30-40% EtOAc in hexanes to give a pale yellow oil (4.43 g, 83% yield). 1H NMR (400 MHz, CDCl3) δ 7.34-7.45 (m, 5 H) 7.19 (s, 1 H) 7.09 (s, 1 H) 5.13 (s, 2 H) 4.96-5.03 (m, 1 H) 3.85 (ddd, J=12.00, 6.95, 3.28 Hz, 1 H) 3.74 (dt, J=12.13, 6.06 Hz, 1 H) 3.27 (dd, J=16.42, 9.60 Hz, 1 H) 3.01 (dd, J=16.42, 7.07 Hz, 1 H) 1.58 (s, 9 H); LCMS for C21H24O5 m/z 357.00 (M+H)+.

Workup

  1. customThe mixture was quenched with H2O (60 mL)
  2. extractionextracted EtOAc (2×60 mL)
  3. washThe organic layers were washed with H2O (2×100 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatograph
  7. washeluting with 30-40% EtOAc in hexanes

Sources & evidence

ORD record
ord-a1df842570f340ada81ddb34eadac232
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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