Propanedioic acid, 2,2-bis(hydroxymethyl)-, 1,3-diethyl ester → Diethyl 2-[(4,4',4''-trimethoxytrityl)oxymethyl]-2-hydroxymethylmalonate

HRID 2417147Notes

Reaction equation

HRID 2417147 reaction equation
[OH:1][CH2:2][C:3]([CH2:14][OH:15])([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH3:16][O:17][C:18]1[CH:41]=[CH:40][C:21]([C:22](Cl)([C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[CH:20][CH:19]=1>N1C=CC=CC=1.O1CCOCC1>[CH3:30][O:29][C:26]1[CH:25]=[CH:24][C:23]([C:22]([O:15][CH2:14][C:3]([CH2:2][OH:1])([C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:9]([O:11][CH2:12][CH3:13])=[O:10])([C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[C:21]2[CH:40]=[CH:41][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)=[CH:28][CH:27]=1

Participants

5

Reactant 2

HCID 311844Propanedioic acid, 2,2-bis(hydroxymethyl)-, 1,3-diethyl esterHCID 6305054,4',4''-Trimethoxytrityl chloride

Product 1

HCID 15539820Diethyl 2-[(4,4',4''-trimethoxytrityl)oxymethyl]-2-hydroxymethylmalonateYield 67.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 312751,4-DioxaneSolvent

Procedure

Referring to scheme 1, diethyl bis-(hydroxymethyl)malonate (11.5 g, 55 mmol) was treated overnight with 4,4′,4″-trimethoxytrityl chloride (19.2 g, 52 mmol) in pyridine (16 mL) and dioxane (100 mL), and the solvent was evaporated. The residue was dissolved in CH2Cl2 (500 mL), washed with 5% aqueous NaHCO3 (3×100 mL), washed with brine (2×100 mL), dried over Na2SO4 and evaporated. The residue was purified on a silica gel column using a step gradient of ethyl acetate (0 to 15%) in toluene to give 1 (8.2 g, 67.5%) as an oil. HR MALDI MS: calculated for C31H36O9 (M+H+) 553.2442, found 553.2438. 1H NMR (CDCl3) δ 7.29 (6H, d, J=8.8 Hz), 6.83 (6H, d, J=8.8 Hz), 4.26-4.11 (6H, m), 3.80 (9H, s), 3.62 (2H, s), 2.11 (1H, t, J=5.8 Hz), 1.24 (6H, t, J=7.0 Hz). 13C NMR (CDCl3) δ 169.3 (C), 158.5 (C), 136.1 (C), 129.8 (CH), 113.2 (CH), 86.0 (C), 63.7 (CH2), 61.9 (CH2), 61.6 (CH2), 60.6 (C), 55.2 (CH3), 14.1 (CH3).

Workup

  1. customthe solvent was evaporated
  2. dissolutionThe residue was dissolved in CH2Cl2 (500 mL)
  3. washwashed with 5% aqueous NaHCO3 (3×100 mL)
  4. washwashed with brine (2×100 mL)
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-2c655e22a8304996b5b8a169a5afe24e
Source dataset
uspto-grants-2004_11
Patent number
US06825338B2

Reaction notes

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