Acetic Acid → 4-(2-Iodophenylamino)piperidine-1-carboxylic acid tert-butyl ester

HRID 552130Notes

Reaction equation

HRID 552130 reaction equation
[I:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[C:9]([N:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1)([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:12]([O:11][C:9]([N:16]1[CH2:21][CH2:20][CH:19]([NH:4][C:3]2[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=2[I:1])[CH2:18][CH2:17]1)=[O:10])([CH3:15])([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 119952-IodoanilineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 436521794-(2-Iodophenylamino)piperidine-1-carboxylic acid tert-butyl esterYield 77.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-iodoaniline (1.100 g, 5.00 mmol), 1-Boc-4-piperidone (1.500 g, 7.50 mmol)), acetic acid (1.0 mL, 17.5 mmol) and sodium triacetoxy borohydride (2.420 g, 11 mmol) in 1,2-dichloroethane (30 mL) was stirred at ambient temperature for 2 days. The reaction was quenched with water, and the organic phase was separated. The aqueous phase was extracted with dichloromethane. The combined organic phase was washed with water, brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash chromatography to afford 4-(2-Iodophenylamino)piperidine-1-carboxylic acid tert-butyl ester (1.560 g, 50%). 1H NMR (300 MHz, CDCl3) δ 7.63 (dd, J=1.5 and 7.8 Hz, 1H), 7.20-7.14 (m, 1H), 6.56 (d, J=8.4 Hz, 1H), 6.41 (dt, J=1.5 and 7.8 Hz, 1H), 3.99-3.95 (m, 2H), 3.48-3.43 (m, 1H), 3.03-2.94 (m, 2H), 2.02-1.97 (m, 2H), 1.52-1.36 (m, 11H).

Workup

  1. customThe reaction was quenched with water
  2. customthe organic phase was separated
  3. extractionThe aqueous phase was extracted with dichloromethane
  4. washThe combined organic phase was washed with water, brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-11adb62659064ad7bcee4d92228fc65c
Source dataset
uspto-grants-2011_05
Patent number
US07951805B2

Reaction notes

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