Hydrochloric Acid → HCID 86597685, compound

HRID 1951690Notes

Reaction equation

HRID 1951690 reaction equation
C(O[C:6](=[O:24])[N:7]([C:9]1[CH:10]=[N:11][C:12]([N:16]2[CH2:20][C@H:19]([OH:21])[CH2:18][C@H:17]2[CH2:22][OH:23])=[CH:13][C:14]=1[I:15])[CH3:8])(C)(C)C.Cl.C(N(C(C)C)C(C)C)C.[F:35][C:36]([F:54])([F:53])[C:37]1[CH:38]=[C:39]([C:47](C)([CH3:51])[C:48](Cl)=O)[CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1>ClCCl.C(OCC)C>[F:35][C:36]([F:53])([F:54])[C:37]1[CH:38]=[C:39]([C:47]([CH3:51])([CH3:48])[C:6]([N:7]([C:9]2[CH:10]=[N:11][C:12]([N:16]3[CH2:20][C@H:19]([OH:21])[CH2:18][C@H:17]3[CH2:22][OH:23])=[CH:13][C:14]=2[I:15])[CH3:8])=[O:24])[CH:40]=[C:41]([C:43]([F:44])([F:45])[F:46])[CH:42]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 112671412-(3,5-Bis(trifluoromethyl)phenyl)-2-methylpropanoyl chlorideHCID 67194876(2S,4R)-[6-(4-Hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-iodo-pyridin-3-yl]-methyl-carbamic acid tert-butyl ester

Product 1

HCID 86597685HCID 86597685, compoundYield 87.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 8.94 g (19.9 mmol) (2S,4R)-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-iodo-pyridin-3-yl]-methyl-carbamic acid tert-butyl ester in 85 ml dichloromethane were added 50 ml of a 2 M solution of hydrogen chloride in diethylether at 0° C. The reaction mixture was stirred at room temperature for 22 h and concentrated in vacuo. The residue was re-dissolved in 85 ml dichloromethane and treated with 17 ml (99.4 mmol) N-ethyldiisopropylamine. At 0° C. 19.0 g (59.7 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionyl chloride were added dropwise. The reaction mixture was stirred at room temperature for 4 h and concentrated in vacuo. After addition of 250 ml methanol and 70 ml 3 N potassium hydroxide solution the mixture was stirred at room temperature for 2 h. The mixture was concentrated to remove methanol and extracted with four 750 ml-portions of dichloromethane. The combined organic layers were washed with 500 ml 1 N sodium hydroxide solution and 500 ml brine, dried over sodium sulfate and evaporated. Flash-chromatography gave 11 g (87%) of the title compound as a light yellow foam.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was re-dissolved in 85 ml dichloromethane
  3. customAt 0° C
  4. stirringThe reaction mixture was stirred at room temperature for 4 h
  5. concentrationconcentrated in vacuo
  6. additionAfter addition of 250 ml methanol and 70 ml 3 N potassium hydroxide solution the mixture
  7. stirringwas stirred at room temperature for 2 h
  8. concentrationThe mixture was concentrated
  9. customto remove methanol
  10. extractionextracted with four 750 ml-portions of dichloromethane
  11. washThe combined organic layers were washed with 500 ml 1 N sodium hydroxide solution and 500 ml brine
  12. dry with materialdried over sodium sulfate
  13. customevaporated

Sources & evidence

ORD record
ord-05dbbaf556ab4aa6ad7f4145f7fcddb5
Source dataset
uspto-grants-2013_03
Patent number
US08404708B2

Reaction notes

Loading…