Triethylamine → 4-[(2-Bromo-2,2-difluoroacetyl)-(2-iodophenyl)amino]piperidine-1-carboxylic acid tert-butyl ester

HRID 552131

Reaction equation

HRID 552131 reaction equation
[Br:1][C:2]([F:7])([F:6])[C:3](Cl)=[O:4].[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[I:28])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].C(N(CC)CC)C>ClCCl>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([N:21]([C:3](=[O:4])[C:2]([Br:1])([F:7])[F:6])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[I:28])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 520892Bromodifluoroacetyl chlorideHCID 436521794-(2-Iodophenylamino)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 671716824-[(2-Bromo-2,2-difluoroacetyl)-(2-iodophenyl)amino]piperidine-1-carboxylic acid tert-butyl esterYield 83.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Bromodifluoroacetyl chloride (0.800 g, 4.1 mmol) was added dropwise to a cooled (0° C.) solution of 4-(2-Iodophenylamino)piperidine-1-carboxylic acid tert-butyl ester (1.500 g, 3.7 mmol) and triethylamine (1.0 mL, 7.1 mmol) in dichloromethane (20 mL). The cooling bath was removed 30 minutes after the addition of all reagents. The reaction mixture was stirred at ambient temperature for 1 hour, then diluted with ethyl acetate, washed with water and brine, dried over anhydrous Na2SO4 and concentrated. Purification of the residue by flash chromatography to afford 4-[(2-bromo-2,2-difluoroacetyl)-(2-iodophenyl)amino]piperidine-1-carboxylic acid tert-butyl ester (1.730 g, 83%). 1H NMR (300 MHz, CDCl3) δ 7.88 (dd, J=1.2 and 7.8 Hz, 1H), 7.41-7.06 (m, 3H), 4.45-4.37 (m, 1H), 4.17-4.03 (m, 2H), 2.81-2.64 (m, 2H), 2.18-2.12 (m, 1H), 1.89-1.84 (m, 1H), 1.59-1.52 (m, 1H), 1.40 (s, 9H), 1.25-0.98 (m, 1H).

Workup

  1. customThe cooling bath was removed 30 minutes
  2. additionafter the addition of all reagents
  3. additiondiluted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customPurification of the residue by flash chromatography

Sources & evidence

ORD record
ord-97851995b6b74204aa007a95ac674fa5
Source dataset
uspto-grants-2011_05
Patent number
US07951805B2

Linked notes

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