1,2-Dimethoxyethane → 4-(2-(Tert-butoxycarbonylamino)benzyl)phthalic acid dimethyl ester

HRID 1357383Notes

Reaction equation

HRID 1357383 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[C:5](=[CH:10][C:11]([CH2:14]Br)=[CH:12][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7].[C:17]([O:21][C:22]([NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O)=[O:23])([CH3:20])([CH3:19])[CH3:18].C(=O)([O-])[O-].[Na+].[Na+].COCCOC>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)Cl.O>[CH3:1][O:2][C:3](=[O:16])[C:4]1[C:5](=[CH:10][C:11]([CH2:14][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[NH:24][C:22]([O:21][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:23])=[CH:12][CH:13]=1)[C:6]([O:8][CH3:9])=[O:7]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 2773226(2-BOC-aminophenyl)boronic acidHCID 232556044-Bromomethylphthalic acid dimethyl ester

Product 1

HCID 699938044-(2-(Tert-butoxycarbonylamino)benzyl)phthalic acid dimethyl ester

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-bromomethylphthalic acid dimethyl ester (3.1 g, 10.8 mmol), 2-(tert-butoxycarbonylamino)phenylboronic acid (4.3 g, 18.1 mmol), tetrakis(triphenylphosphine)-palladium(0) (0.6 g), 2 M aqueous sodium carbonate (20 ml), and 1,2-dimethoxyethane (40 ml) was heated at 90° C. for 19 hours. The reaction mixture was cooled to room temperature and partioned between water (60 ml) and methylene chloride (60 ml). The organic phase was isolated, washed with water (2×50 ml), dried over magnesium sulphate, and evaporated to dryness in vacuo. The crude product was purified on silica gel (eluent: methylene chloride:ethyl acetate (95:5) to give 4-[2-(tert-butoxycarbonylamino)benzyl]phthalic acid dimethyl ester as yellow crystals (yield: 1.49 g, (40%)). 1H—NMR (CDCl3) in ppm: δ 7.70 (1H,d); 7.67 (1H,d); 7.47 (1H,d); 7.22-7.33 (2H,m); 7.10 (2H,d); 6.05 (1H,s); 4.03 (2H,s); 3.9 (6H,2xs); 1.47 (9H,s).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic phase was isolated
  3. washwashed with water (2×50 ml)
  4. dry with materialdried over magnesium sulphate
  5. customevaporated to dryness in vacuo
  6. customThe crude product was purified on silica gel (eluent

Sources & evidence

ORD record
ord-e8fbc18d38fd47d39dcc5ee4d9812391
Source dataset
uspto-grants-2003_07
Patent number
US06590118B1

Reaction notes

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