Trifluoroacetic acid → 2-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

HRID 897927Notes

Reaction equation

HRID 897927 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([B:9]2[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]2)[CH:6]=[CH:5][C:4]=1[NH:18]C(=O)OC(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([B:9]2[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]2)[CH:6]=[CH:5][C:4]=1[NH2:18]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 177502214-(tert-Butoxycarbonylamino)-3-methoxyphenylboronic acid, pinacol ester

Product 1

HCID 177502072-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineYield 67.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

A mixture of tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (45.0 g, 0.129 mol) was dissolved in dichloromethane (270 mL) then the solution was cooled to 5° C. in and ice bath. A mixture of 20% trifluoroacetic acid in dichloromethane was added dropwise over the course of one hour while maintaining the temperature of the mixture at <5° C. The reaction mixture was warmed to ambient temperature and stirred for 2 hours. The solvents were removed under reduced pressure then the resulting oil was dissolved in dichloromethane (250 mL) and cautiously extracted with 2.5 N aqueous sodium hydroxide (300 mL) then brine (100 mL). The organic solution was dried over magnesium sulfate, filtered and the fitrate concentrated under reduced pressure to give 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (21.7 g, 67.5%) as a light brown solid bismaleate: 1H NMR (DMSO-d6, 400 MHz) δ 7.06 (d, 1H), 6.98 (s, 1H), 8.09 (d, 1H), 6.59 (d, 1H), 5.13 (bs, 2H), 3.76 (s, 3H), 1.26 (s, 12H); RP-HPLC (Hypersil HS C18 Hypersil HS C18, 5 μm, 100 A, 250×4.6 mm; 25%-100% acetonitrile-0.05 M ammonium acetate over 10 min, 1 mL/min) tr 10.85 min.

Workup

  1. additionwas added dropwise over the course of one hour
  2. temperaturewhile maintaining the temperature of the mixture at <5° C
  3. temperatureThe reaction mixture was warmed to ambient temperature
  4. customThe solvents were removed under reduced pressure
  5. dissolutionthe resulting oil was dissolved in dichloromethane (250 mL)
  6. extractioncautiously extracted with 2.5 N aqueous sodium hydroxide (300 mL)
  7. dry with materialThe organic solution was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationthe fitrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-eefa0e90ba76434bb00820c035703d06
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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