Boron tribromide → 3-{2-Fluoro-4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one

HRID 2263444Notes

Reaction equation

HRID 2263444 reaction equation
C([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:32]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=2)[S:15][C:16]=1[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[NH:29][C:28](=[O:30])[O:27][N:26]=2)=[C:21]([F:31])[CH:20]=1)C1C=CC=CC=1.B(Br)(Br)Br.ClCCl.CC(C)=O.C([O-])(O)=O.[Na+]>ClCCl.CO>[F:31][C:21]1[CH:20]=[C:19]([O:18][CH2:17][C:16]2[S:15][C:14]([C:32]3[CH:37]=[CH:36][C:35]([C:38]([F:40])([F:41])[F:39])=[CH:34][CH:33]=3)=[N:13][C:12]=2[CH2:11][CH2:10][CH2:9][OH:8])[CH:24]=[CH:23][C:22]=1[C:25]1[NH:29][C:28](=[O:30])[O:27][N:26]=1

Participants

7

Reactant 4

HCID 25134Boron tribromide2×HCID 516892Sodium BicarbonateHCID 21584124Propan-2-one--dichloromethane (1/1)HCID 1361499453-{4-[4-(3-Benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-phenyl}-4H-[1,2,4]oxadiazol-5-one

Product 1

HCID 1361499883-{2-Fluoro-4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a stirred solution of 100 mg of 3-{4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-phenyl}-4H-[1,2,4]oxadiazol-5-one in 3 mL of dichloromethane at −70° C. was added 0.34 mL of a 1M solution of boron tribromide in dichloromethane. After 1 h at −60° C., TLC monitoring (dichloromethane/acetone 8/2) showed remaining starting material so 1 mL of a 1M solution of boron tribromide in dichloromethane was added. After 10 min, the reaction mixture was poured into 30 mL of methanol and was neutralised with 5 mL of a saturated aqueous solution of NaHCO3. The suspension was filtered and the filtrate was concentrated under reduced pressure. The residue was taken up into dichloromethane then water added. The aqueous layer was separated and extracted three times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 60 mg of crude product. Purification by column chromatography on silica gel (dichloromethane 1/acetone 1) gave 13 mg of a first batch of the title compound (purity >95%) and 50 mg of a second batch of the title compound (purity >90%). The second batch was repurified by column chromatography on silica gel (dichloromethane 90/methanol 10). A total of 48 mg of 3-{2-fluoro-4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one was obtained.

Workup

  1. additionwas added
  2. waitAfter 10 min
  3. filtrationThe suspension was filtered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. additionwater added
  6. customThe aqueous layer was separated
  7. extractionextracted three times with dichloromethane
  8. dry with materialThe combined organic layers were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give 60 mg of crude product
  12. customPurification by column chromatography on silica gel (dichloromethane 1/acetone 1)

Sources & evidence

ORD record
ord-bc511209c51c42b1938ea29532701ecb
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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