Trifluoroacetic acid → Ethyl 2-[4-[2-(methanesulfonamido)ethylamino]cyclohexyl]acetate

HRID 1404364Notes

Reaction equation

HRID 1404364 reaction equation
O=[C:2]1[CH2:7][CH2:6][CH:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:3]1.[NH2:14][CH2:15][CH2:16][NH:17][S:18]([CH3:21])(=[O:20])=[O:19].FC(F)(F)C(O)=O.C(N(CC)CC)C.[BH4-].[Na+].C([O-])([O-])=O.[Na+].[Na+]>ClCCl.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[CH3:21][S:18]([NH:17][CH2:16][CH2:15][NH:14][CH:2]1[CH2:7][CH2:6][CH:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:3]1)(=[O:20])=[O:19]

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 533845N-(2-Aminoethyl)methanesulfonamideHCID 4311764Sodium borohydrideHCID 12666966Ethyl 2-(4-oxocyclohexyl)acetate

Product 1

HCID 86722969Ethyl 2-[4-[2-(methanesulfonamido)ethylamino]cyclohexyl]acetate

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a mixture of ethyl 2-(4-oxocyclohexyl)acetate (736 mg, 4 mmol) and N-(2-aminoethyl)methanesulfonamide; 2,2,2-trifluoroacetic acid salt (1.26 g, 5 mmol) in dichloromethane (6 mL) was added triethylamine (690 μL, 5 mmol) followed by Titanium (IV) ethoxide (420 μL, 2 mmol, technical grade). The resulting cloudy mixture was stirred for 4 hours then concentrated under reduced pressure. The residue was taken up in methanol (6 mL). This mixture was cooled to −78° C. To the resulting mixture was added sodium borohydride (187 mg, 4.8 mmol). On complete addition, the cold bath was allowed to expire and stirring continued for 15.5 hours. The resulting mixture was concentrated under reduced pressure to give a thick paste. This residue was taken up in dichloromethane (40 mL). To this mixture was added Na2CO3 (5.5 mL, saturated aqueous solution). The resulting mixture was stirred for 5 minutes. To this mixture was added celite (1.8 g). This mixture was stirred for 5 minutes then filtered through a pad of celite. The filtrate is washed with saturated aqueous Na2CO3, dried over magnesium sulfate and concentrated to give the title compound as a 6:1 mixture of trans:cis isomers. This material was used without further purification.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. additionOn complete addition
  3. stirringstirring
  4. waitcontinued for 15.5 hours
  5. concentrationThe resulting mixture was concentrated under reduced pressure
  6. customto give a thick paste
  7. stirringThe resulting mixture was stirred for 5 minutes
  8. additionTo this mixture was added celite (1.8 g)
  9. stirringThis mixture was stirred for 5 minutes
  10. filtrationthen filtered through a pad of celite
  11. washThe filtrate is washed with saturated aqueous Na2CO3
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-1d27cf2363774c90b0ebc2f35a0cd232
Source dataset
uspto-grants-2014_12
Patent number
US08912169B2

Reaction notes

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