1-Hydroxybenzotriazole → tert-butyl[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-carbamate

HRID 1943305Notes

Reaction equation

HRID 1943305 reaction equation
Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.[C:32]([O:36][C:37]([NH:39][C@@H:40]([CH2:44][CH:45]1[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1)[C:41]([OH:43])=O)=[O:38])([CH3:35])([CH3:34])[CH3:33].[C@:51]12([CH3:61])[C:57]([CH3:59])([CH3:58])[CH:54]([CH2:55][CH2:56]1)[CH2:53][CH:52]2[NH2:60]>CN(C=O)C>[C:32]([O:36][C:37](=[O:38])[NH:39][C@H:40]([C:41](=[O:43])[NH:60][C@H:52]1[CH2:53][C@@H:54]2[C:57]([CH3:59])([CH3:58])[C@@:51]1([CH3:61])[CH2:56][CH2:55]2)[CH2:44][CH:45]1[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1)([CH3:33])([CH3:34])[CH3:35]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 211083(R)-bornylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10588189(2S)-2-(((tert-butoxy)carbonyl)amino)-3-cyclohexylpropanoic acid

Product 1

HCID 131730275tert-butyl[(S)-2-cyclohexyl-1-((1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylcarbamoyl)-ethyl]-carbamateYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3.53 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (18.4 mmol, 1.0 equiv.), 1.25 g of 1-hydroxybenzotriazole (9.2 mmol, 0.5 equiv.) and 7.3 ml of Hünig's base were added to a solution of 5.0 g of (S)-2-tert-butoxycarbonylamino-3-cyclohexylpropionic acid (Boc-Cha-OH, 18.4 mmol, 1.0 equiv.) in DMF (60 ml) at 0° C. under argon, and the mixture was stirred for 30 min. Then 2.83 g of (R)-(+)-bornylamine (18.4 mmol, 1.0 equiv.) and 3.7 ml of Hünig's base were added, and the mixture was stirred at RT for 16 h. The reaction mixture was quenched with NaHCO3 (saturated, aq.) and extracted three times with ethyl acetate. The combined organic phases were washed twice with water and dried over Na2SO4 and concentrated. Purification by flash chromatography on silica gel with heptane/ethyl acetate mixtures as eluent afforded 6.58 g (88% yield) of the title compound as a colorless oil.

Workup

  1. stirringthe mixture was stirred at RT for 16 h
  2. customThe reaction mixture was quenched with NaHCO3 (saturated, aq.)
  3. extractionextracted three times with ethyl acetate
  4. washThe combined organic phases were washed twice with water
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by flash chromatography on silica gel with heptane/ethyl acetate

Sources & evidence

ORD record
ord-a6acb47249c7472e97faca093072d3ff
Source dataset
uspto-grants-2013_03
Patent number
US08389764B2

Reaction notes

Loading…