Toluene → (9S,13R)-13-methyl-13-(4,4,4-trifluorobutyl)-7,14-dioxa-2,18-dithia-5,19-diazatricyclo[14.2.1.05,9]nonadeca-1(19),10,16-triene-6,15-dione

HRID 1888318Notes

Reaction equation

HRID 1888318 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][CH2:8][S:9][C:10]2[S:11][CH:12]=[C:13]([C:15]([OH:17])=[O:16])[N:14]=2)[C@@H:5](/[CH:18]=[CH:19]/[CH2:20][C:21](O)([CH3:29])[CH2:22][CH2:23][CH2:24][C:25]([F:28])([F:27])[F:26])[CH2:4][O:3]1.C(N(CC)CC)C.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.C1(C)C=CC=CC=1>O1CCCC1>[CH3:29][C@:21]1([CH2:22][CH2:23][CH2:24][C:25]([F:27])([F:26])[F:28])[O:16][C:15](=[O:17])[C:13]2[N:14]=[C:10]([S:11][CH:12]=2)[S:9][CH2:8][CH2:7][N:6]2[C@H:5]([CH2:4][O:3][C:2]2=[O:1])[CH:18]=[CH:19][CH2:20]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 8471TriethylamineHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 668588202-[(2-{(4S)-2-oxo-4-[(1E)-8,8,8-trifluoro-4-hydroxy-4-methyl-1-octenyl]-1,3-oxazolidin-3-yl}ethyl)sulfanyl]-1,3-thiazole-4-carboxylic acid

Product 1

HCID 66857374(9S,13R)-13-methyl-13-(4,4,4-trifluorobutyl)-7,14-dioxa-2,18-dithia-5,19-diazatricyclo[14.2.1.05,9]nonadeca-1(19),10,16-triene-6,15-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the compound 45-4 (208 mg) in anhydrous tetrahydrofuran (5.0 mL) were added triethylamine (0.08 mL), 2,4,6-trichlorobenzoylchloride (0.08 mL) at 0° C. The solution was stirred for 1 Hour and then 30 minutes at room temperature. Anhydrous toluene (45.0 mL) was added to the reaction solution, which was filtrated. The obtain filtrate was added to a solution of 4-(dimethylamino)pyridine (272 mg) in anhydrous toluene (45.0 ml) with heating to reflux and the solution was allowed to return to room temperature. 1N hydrochloric acid was added to the reaction solution, which was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated. The obtained residue was purified by column chromatography on silica gel (Fuji-silysia, FL60D, 75 cc, hexane:ethyl acetate=4:1) to give the title compound (less polar:83.9 mg, more polar:75.0 mg) having the following physical data.

Workup

  1. custom30 minutes
  2. customat room temperature
  3. filtrationwas filtrated
  4. additionThe obtain filtrate was added to a solution of 4-(dimethylamino)pyridine (272 mg) in anhydrous toluene (45.0 ml)
  5. temperaturewith heating
  6. temperatureto reflux
  7. customto return to room temperature
  8. addition1N hydrochloric acid was added to the reaction solution, which
  9. extractionwas extracted with ethyl acetate
  10. washThe organic layer was washed with water and brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. concentrationconcentrated
  13. customThe obtained residue was purified by column chromatography on silica gel (Fuji-silysia, FL60D, 75 cc, hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-bc01021b95464ebfa83703735bb1663b
Source dataset
uspto-grants-2013_08
Patent number
US08501793B2

Reaction notes

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