2,2,2-Trifluoroethanol → HCID 178523334, compound

HRID 504069Notes

Reaction equation

HRID 504069 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].Cl[C:8](OC1C=CC([N+]([O-])=O)=CC=1)=[O:9].CCN(C(C)C)C(C)C.[CH:29]1([CH2:32][O:33][C:34]2[CH:35]=[C:36]3[C:41](=[CH:42][CH:43]=2)[C:40]([CH:44]2[CH2:49][O:48][CH:47]([CH2:50][CH2:51][CH2:52][NH2:53])[O:46][CH2:45]2)=[CH:39][CH:38]=[CH:37]3)[CH2:31][CH2:30]1>ClCCl.ClCCCl>[CH:29]1([CH2:32][O:33][C:34]2[CH:35]=[C:36]3[C:41](=[CH:42][CH:43]=2)[C:40]([C@@H:44]2[CH2:49][O:48][C@@H:47]([CH2:50][CH2:51][CH2:52][NH:53][C:8](=[O:9])[O:4][CH2:3][C:2]([F:6])([F:5])[F:1])[O:46][CH2:45]2)=[CH:39][CH:38]=[CH:37]3)[CH2:30][CH2:31]1

Participants

7

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 81531Diisopropylethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 21930228HCID 21930228, compound

Product 1

HCID 178523334HCID 178523334, compoundYield 27.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

0.075 ml (1.01 mmol) of 2,2,2-trifluoroethanol is added, dropwise and at ambient temperature, to a suspension of 0.205 g (1.01 mmol) of 4-nitrophenyl chloroformate and 0.555 g (2.02 mmol) N,N-diisopropylaminoethylpolystyrene (Ps-DIEA, 2% DVB, titre=3.66 mmol/g) in 7.1 ml of dichloromethane. The mixture is stirred with orbital shaking and at ambient temperature for 16 hours. The resin is filtered through a cartridge equipped with a sintered glass funnel and rinsing is carried out with 4 ml of dichloromethane. The filtrate is concentrated under reduced pressure and the oily residue thus obtained is taken up in 3.5 ml of 1,2-dichloroethane. 0.134 ml (0.78 mmol) of N,N-diisopropylethylamine and 0.205 g (0.6 mmol) of 3-[5-(6-cyclopropylmethoxynaphthalen-1-yl)-1,3-dioxan-2-yl]propylamine are successively added. This reaction mixture is heated at 60° C. for 16 hours. After cooling, washing is carried out with 20 ml of a 1N sodium hydroxide solution. The phases are separated and the organic phase is filtered through a hydrophobic sintered glass funnel. The filtrate is concentrated under reduced pressure and the residue is purified by chromatography on silica gel, eluting with an 80/20 mixture of cyclohexane and ethyl acetate. After washing in 5 ml of diisopropyl ether, 0.076 g of white solid is obtained.

Workup

  1. stirringwith orbital shaking and at ambient temperature for 16 hours
  2. filtrationThe resin is filtered through a cartridge
  3. customequipped with a sintered glass funnel
  4. washrinsing
  5. concentrationThe filtrate is concentrated under reduced pressure
  6. customthe oily residue thus obtained
  7. temperatureAfter cooling
  8. washwashing
  9. customThe phases are separated
  10. filtrationthe organic phase is filtered through a hydrophobic sintered glass funnel
  11. concentrationThe filtrate is concentrated under reduced pressure
  12. customthe residue is purified by chromatography on silica gel
  13. washeluting with an 80/20 mixture of cyclohexane and ethyl acetate
  14. washAfter washing in 5 ml of diisopropyl ether

Sources & evidence

ORD record
ord-aa1e7f2dcbd34cf8b9f3abd72ab506e5
Source dataset
uspto-grants-2010_08
Patent number
US07777057B2

Reaction notes

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