Hydrochloric Acid → HCID 178490596, compound

HRID 1508594Notes

Reaction equation

HRID 1508594 reaction equation
[OH2:1].[OH-:2].[Li+].[F:4][C:5]1([F:51])[CH2:8][N:7]([C:9]2[N:14]=[C:13]([CH2:15][N:16]3[C@@H:20]([CH3:21])[C@@H:19]([C:22]4[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[C:24]([F:32])[CH:23]=4)[O:18][C:17]3=[O:33])[C:12]([C:34]3[CH:35]=[C:36](OC(C4CCCCC4)=O)[CH:37]=[CH:38][C:39]=3[O:40][CH3:41])=[CH:11][CH:10]=2)[CH2:6]1.Cl.[C:53](#N)[CH3:54]>O.O1CCOCC1.C(#N)C.O>[F:51][C:5]1([F:4])[CH2:6][N:7]([C:9]2[N:14]=[C:13]([CH2:15][N:16]3[C@@H:20]([CH3:21])[C@@H:19]([C:22]4[CH:27]=[C:26]([C:28]([F:30])([F:29])[F:31])[CH:25]=[C:24]([F:32])[CH:23]=4)[O:18][C:17]3=[O:33])[C:12]([C:34]3[CH:35]=[C:36]([C@H:11]4[CH2:12][CH2:13][C@H:53]([C:54]([OH:2])=[O:1])[CH2:9][CH2:10]4)[CH:37]=[CH:38][C:39]=3[O:40][CH3:41])=[CH:11][CH:10]=2)[CH2:8]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 168937Lithium hydroxide, monohydrateHCID 86704643HCID 86704643, compound

Product 1

HCID 178490596HCID 178490596, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A solution of lithium hydroxide monohydrate (154 mg, 3.67 mmol) in water (4 ml) was added into a solution of methyl trans-4-({3-[6-(3,3-difluoroazetidin-1-yl)-2-({(4S,5R)-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}cyclohexanecarboxylate (507 mg, 0.733 mmol) in 1,4-dioxane (6 ml) at room temperature and stirred overnight. To the resulting crude was added HCl (1N, aq.) until the mixture turned cloudy. This cloudiness was dissolved by addition of acetonitrile. This clear solution was purified by preparative HPLC (reverse phase, Waters SunFire PrepC18 OBD 5 um 19×150 mm) eluting with acetonitrile/water+0.05% HCOOH (30% to 100% organic in 10 min, hold 100% for 2 min, 20 mL/min). Related fractions were pooled and evaporated under reduced pressure to afford a colorless glass. This glass was re-dissolved in an acetonitrile/water mixture and lyophilized overnight to afford a fluffy white solid of 430.5 mg as the titled compound. LCMS calc.=677.23. found=678.44 (M+1)+. 1H-NMR (CD3OD, 500 MHz) δ 7.47-7.42 (m, 2H), 7.40 (d, J=8.5 Hz, 1H), 7.34 (br d, J=8.5 Hz, 1H), 7.22 (dd, J=8.5, 2.5 Hz, 1H), 7.06-6.94 (br m, 2H), 6.54 (d, J=8.5 Hz, 1H), 5.71-5.58 (br m, 1H), 4.68-4.53 (br m, 1H), 4.39 (d, J=12.5 Hz, 2H), 4.36 (d, J=12 Hz, 2H), 4.28-4.18 (br s, 0.5H), 4.16-4.02 (br m, 1H), 3.96-3.86 (br m, 0.5H), 3.74 (s, 3H), 2.50 (s, 1H), 2.32 (s, 1H), 2.11-2.04 (m, 2H), 1.96-1.88 (br m, 2H), 1.60-1.44 (m, 4H), 0.65 (br s, 1.6H), 0.54 (br s, 1.4H).

Workup

  1. customThis clear solution was purified by preparative HPLC (reverse phase, Waters SunFire PrepC18 OBD 5 um 19×150 mm)
  2. washeluting with acetonitrile/water+0.05% HCOOH (30% to 100% organic in 10 min, hold 100% for 2 min, 20 mL/min)
  3. customevaporated under reduced pressure
  4. customto afford a colorless glass
  5. waitlyophilized overnight

Sources & evidence

ORD record
ord-3e442327fd864d55867a0125b32a9533
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

Loading…