Cyclohexanecarboxylic acid → Tert-butyl 3-(3-(cyclohexanecarboxamido)phenyl)propylcarbamate

HRID 1189930Notes

Reaction equation

HRID 1189930 reaction equation
[CH:1]1([C:7]([OH:9])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)C(C)C)C.C1(C[NH:48][C:49]2[CH:50]=[C:51]([CH2:55][CH2:56][CH2:57][NH:58][C:59](=[O:65])[O:60][C:61]([CH3:64])([CH3:63])[CH3:62])[CH:52]=[CH:53][CH:54]=2)CCCCC1>CN(C=O)C.O>[CH:1]1([C:7]([NH:48][C:49]2[CH:50]=[C:51]([CH2:55][CH2:56][CH2:57][NH:58][C:59](=[O:65])[O:60][C:61]([CH3:63])([CH3:62])[CH3:64])[CH:52]=[CH:53][CH:54]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 7413Cyclohexanecarboxylic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59317002Tert-butyl 3-(3-(cyclohexylmethylamino)phenyl)propylcarbamate

Product 1

HCID 59316922Tert-butyl 3-(3-(cyclohexanecarboxamido)phenyl)propylcarbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of cyclohexanecarboxylic acid (21) (0.23 ml, 1.79 mmol), TBTU (0.56 g, 1.74 mmol) and iPr2EtN (0.33 ml, 1.89 mmol) in DMF (20 ml) was added tert-butyl 3-(3-(cyclohexylmethylamino)phenyl)propylcarbamate (17) (0.40 g, 1.59 mmol) in DMF (5 ml). The mixture was stirred at room temperature for 18 h and then diluted with water. The solution was extracted with ethyl acetate and the combined extracts were washed with water, aqueous NaHCO3 and brine, dried over Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (5 to 50% EtOAc-hexanes gradient) gave tert-butyl 3-(3-(cyclohexanecarboxamido)phenyl)propylcarbamate (22) as a colorless oil. Yield (0.455 g, 78%); Yield (0.2 g, 32%); 1H NMR (400 MHz, CDCl3) δ 7.43 (br s, 1H), 7.26-7.28 (m, 2H), 7.20 (t, J=7.6 Hz, 1H), 7.08 (br s, 1H), 6.89-6.91 (m, 1H), 3.12 (t, J=6.0 Hz, 2H), 2.61 (t, J=8.4 Hz, 2H), 2.17-2.23 (m, 1H), 1.93-1.96 (m, 2H), 1.74-1.86 (m, 3H), 1.65-1.72 (m, 2H), 1.48-1.59 (m, 1H), 1.31-1.42 (m, 2H), 1.43 (s, 9H), 1.22-1.38 (m, 4H).

Workup

  1. extractionThe solution was extracted with ethyl acetate
  2. washthe combined extracts were washed with water, aqueous NaHCO3 and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash chromatography (5 to 50% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-ba9174da36814b1fb6d4cfa62d16058f
Source dataset
uspto-grants-2014_03
Patent number
US08674137B2

Reaction notes

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