Methyl iodide → 4-(4-Methanesulfonyl-phenoxy)-2-methoxymethyl-2,3-dihydro-benzofuran-6-carboxylic acid tert-butyl ester

HRID 1643670

Reaction equation

HRID 1643670 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([C:10]1[CH:20]=[C:19]([O:21][C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)[C:13]2[CH2:14][CH:15]([CH2:17][OH:18])[O:16][C:12]=2[CH:11]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:32]I>C1COCC1>[C:3]([O:7][C:8]([C:10]1[CH:20]=[C:19]([O:21][C:22]2[CH:23]=[CH:24][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][CH:27]=2)[C:13]2[CH2:14][CH:15]([CH2:17][O:18][CH3:32])[O:16][C:12]=2[CH:11]=1)=[O:9])([CH3:5])([CH3:6])[CH3:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 595603482-Hydroxymethyl-4-(4-methanesulfonyl-phenoxy)-2,3-dihydro-benzofuran-6-carboxylic acid tert-butyl ester

Product 1

HCID 595599404-(4-Methanesulfonyl-phenoxy)-2-methoxymethyl-2,3-dihydro-benzofuran-6-carboxylic acid tert-butyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

NaH (50 mg, 60% in mineral oil, 1.3 mmol) was added to a solution of 2-hydroxymethyl-4-(4-methanesulfonyl-phenoxy)-2,3-dihydro-benzofuran-6-carboxylic acid tert-butyl ester (200g) (409 mg, 0.97 mmol) in THF (5 mL). The resulting mixture was stirred at 0° C. for 10 min and then methyl iodide (80 uL, 1.3 mmol) was added. The mixture was stirred at room temperature for 2 hr and then quenched with H2O (20 mL), extracted with EtOAc (2×20 mL). The organic layers were dried over MgSO4 and concentrated. The residue was purified by flash column chromatograph eluting with 20-30% EtOAc in hexanes to give a colorless oil (295 mg, 70% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ 1.56 (s, 9 H) 2.89 (dd, J=16.55, 7.20 Hz, 1 H) 3.07 (s, 3 H) 3.08-3.17 (m, 1 H) 3.39-3.44 (m, 3 H) 3.58 (d, J=5.05 Hz, 2 H) 4.99-5.08 (m, 1 H) 7.04-7.10 (m, 2 H) 7.21 (d, J=1.01 Hz, 1 H) 7.30 (d, J=1.26 Hz, 1 H) 7.86-7.93 (m, 2 H); LCMS for C22H26O7S m/z 457.00 (M+Na)+.

Workup

  1. stirringThe mixture was stirred at room temperature for 2 hr
  2. customquenched with H2O (20 mL)
  3. extractionextracted with EtOAc (2×20 mL)
  4. dry with materialThe organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatograph
  7. washeluting with 20-30% EtOAc in hexanes

Sources & evidence

ORD record
ord-3f20ceb878d3425f84d83fe6f165757d
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Linked notes

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