1,2-Dichloroethane → tert-Butyl 4-(2-(4-bromo-2-hydroxyphenylamino)-2-oxoethyl)piperidine-1-carboxylate

HRID 1429545Notes

Reaction equation

HRID 1429545 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]([OH:17])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][C:20]=1[OH:26].C(Cl)CCl>C(#N)C>[Br:25][C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:15](=[O:17])[CH2:14][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)=[C:20]([OH:26])[CH:21]=1

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 1512539[1-(tert-Butoxycarbonyl)piperidin-4-yl]acetic acidHCID 143206052-Amino-5-bromophenol

Product 1

HCID 67466547tert-Butyl 4-(2-(4-bromo-2-hydroxyphenylamino)-2-oxoethyl)piperidine-1-carboxylateYield 48.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid (0.5 g, 2.055 mmol) in acetonitrile (6 mL) was added 2-amino-5-bromophenol (0.421 g, 2.24 mmol), followed by EDC (0.508 g, 2.65 mmol). The mixture was stirred at rt overnight. It was quenched with NH4Cl (aq, sat, 5 mL). The organic layer was separated; the aqueous layer was back extracted with EtOAc (3×5 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 60% EtOAc) to afford Compound 29A as a light yellow oil (412 mg, 47% yield). 1H NMR (500 MHz, CDCl3) δ 8.96 (s, 1H), 7.65 (s, 1H), 7.17 (d, J=1.9 Hz, 1H), 7.03-6.91 (m, 2H), 2.83-2.66 (m, 2H), 2.36 (d, J=7.1 Hz, 2H), 2.10 (m, 2H), 1.76 (d, J=12.6 Hz, 2H), 1.46 (s, 9H), 1.23-1.13 (m, 2H). LCMS (m/z)=414 (M+H)+.

Workup

  1. customIt was quenched with NH4Cl (aq, sat, 5 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was back extracted with EtOAc (3×5 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 60% EtOAc)

Sources & evidence

ORD record
ord-2a5603d35941421aaf933d32cd0f7b17
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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