Imidazole → [2-Benzyloxy-4-(tert-butyldimethylsilanyloxy)-phenylamino]-acetic Acid Tert-butyl Ester

HRID 660511Notes

Reaction equation

HRID 660511 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH:12]=[CH:11][C:10]=1[NH2:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].C(=O)([O-])[O-].[K+].[K+].C([Si](C)(C)Cl)(C)(C)C.N1C=CN=C1.CN(C1C=CC=CN=1)C>CN(C=O)C.CCOC(C)=O>[C:29]([O:28][C:26](=[O:27])[CH2:25][NH:23][C:10]1[CH:11]=[CH:12][C:13]([O:15][Si:16]([C:19]([CH3:20])([CH3:22])[CH3:21])([CH3:17])[CH3:18])=[CH:14][C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([CH3:32])([CH3:31])[CH3:30]

Participants

9

Reactant 6

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 218852-DimethylaminopyridineHCID 28928tert-Butyldimethylsilyl chlorideHCID 79177tert-Butyl bromoacetate2×HCID 688401272-Benzyloxy-4-(tert-butyldimethylsilanyloxy)-phenylamine

Product 1

HCID 68838201[2-Benzyloxy-4-(tert-butyldimethylsilanyloxy)-phenylamino]-acetic Acid Tert-butyl Ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of 2-benzyloxy-4-(tert-butyldimethylsilanyloxy)-phenylamine, t-butyl bromoacetate (3.8 mL, 25.7 mmol), and potassium carbonate (7.1 g, 51.4 mmol) in DMF (20 mL) is heated at 60° C. for 18 h. Additional t-butyl bromoacetate (1 mL) is added and the mixture is stirred and heated for an additional 5 h. The mixture is poured into EtOAc and extracted once with water and four times with brine. The organic phase is dried over magnesium sulfate and the solvent removed under reduced pressure to furnish an oil consisting of product and desilylated product. A solution of this material, t-butyldimethychlorosilane (3.87 g, 25.7 mmol), imidazole (2.33 g, 34.2 mmol), and dimethylaminopyridine (3 mg) in DMF (15 mL) is stirred at RT for 18 h. This solution is poured into EtOAc and extracted with water (1×) and brine (5×). The organic phase is dried over magnesium sulfate and the solvent removed under reduced pressure to afford crude product, which is chromatographed on silica gel to afford the title compound: 1H NMR (CDCl3δ 7.27 (m, 5H), 6.26 (m, 3H), 4.96 (s, 2H), 4.45 (br s, 1H), 3.91 (s, 2H), 1.35 (s, 9H), 0.84 (s, 9H), 0.00 (s, 6H); (M+1)+=444.

Workup

  1. temperatureheated for an additional 5 h
  2. extractionextracted once with water and four times with brine
  3. dry with materialThe organic phase is dried over magnesium sulfate
  4. customthe solvent removed under reduced pressure
  5. customto furnish an oil
  6. extractionextracted with water (1×) and brine (5×)
  7. dry with materialThe organic phase is dried over magnesium sulfate
  8. customthe solvent removed under reduced pressure
  9. customto afford crude product, which
  10. customis chromatographed on silica gel

Sources & evidence

ORD record
ord-ced8dd13043649b3bf6bebf7669cd572
Source dataset
uspto-grants-2011_12
Patent number
US08084448B2

Reaction notes

Loading…