Pyridine → HCID 5327777, compound

HRID 369744Notes

Reaction equation

HRID 369744 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:16]([NH:19][C:20](C2C=CC=CC=2)(C2C=CC=CC=2)[C:21]2[CH:26]=CC=CC=2)=[CH:17][CH:18]=1)[C:5]([OH:15])([C:10]#[C:11][CH:12]1[CH2:14][CH2:13]1)[C:6]([F:9])([F:8])[F:7].N1C=CC=CC=1.BrC(C)C(Br)=[O:48]>CCOCC>[Cl:1][C:2]1[CH:18]=[CH:17][C:16]2[NH:19][C:20](=[O:48])[C@H:21]([CH3:26])[O:15][C@:5](/[CH:10]=[CH:11]/[CH:12]3[CH2:14][CH2:13]3)([C:6]([F:9])([F:8])[F:7])[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 79047Propanoyl bromide, 2-bromo-HCID 15363077HCID 15363077, compound

Product 1

HCID 5327777HCID 5327777, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a stirred ice-cooled solution of 987 mg of trans-6-amino-3-chloro-α-cyclopropyletheayl-α-(trifluoromethyl)benzyl alcohol (from Example 5, Part B) in 50 mL of dry ether was added 0.350 mL of dry pyridine aid 1.66 g of α-bromopropionyl bromide. The cooling bath was removed and then after 30 min at ambient temperature, the reacation mixture was diluted with ether, washed with water and aqueous sodium bicarbonate, dried and evaporated. The residte was dissolved in 50 mL of dry DMF, 2.35 g of lithium iodide and 2.3 g of cesium carbonate was added, and the resulting heterogeneous mixture was stirred at room temperature for 3 days. The reaction mixture was then poured onto water and extracted twice with ether. The combined extracts were washed with water and brine, dried and evaporated to crude product. The title compound was obtained by crystallization from ethyl acetate/hexanes, and recrystallization from ethyl acetate afforded 650 mg of pure title corpound: mp 171-172°; HRMS: Calcd. for C16H168NO2F3Cl (M+H)+ : 346.082166. Found: 346.080681: mp 147-147.5°; HRMS: Calcd. for C17H18NO2F3Cl (M+H)+ : 360.097816. Found: 360.097869

Workup

  1. customThe cooling bath was removed
  2. additionthe reacation mixture was diluted with ether
  3. washwashed with water and aqueous sodium bicarbonate
  4. customdried
  5. customevaporated
  6. dissolutionThe residte was dissolved in 50 mL of dry DMF
  7. addition2.35 g of lithium iodide and 2.3 g of cesium carbonate was added
  8. additionThe reaction mixture was then poured onto water
  9. extractionextracted twice with ether
  10. washThe combined extracts were washed with water and brine
  11. customdried
  12. customevaporated to crude product

Sources & evidence

ORD record
ord-08b8c6d4787c42c0b127dc33ae7c57de
Source dataset
uspto-grants-2000_10
Patent number
US06140320

Reaction notes

Loading…