Tetrahydrofuran → HCID 86627643, compound

HRID 604693Notes

Reaction equation

HRID 604693 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:31]=[C:30](Cl)[CH:29]=[CH:28][C:27]=4[F:33])=[N:24][CH:23]=[CH:22][N:21]=3)[C@H:14]2[CH3:34])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:37][C:38]1[CH:39]=[C:40]([CH:45]=[CH:46][C:47]=1B1OC(C)(C)C(C)(C)O1)[C:41]([O:43][CH3:44])=[O:42].C([O-])([O-])=O.[K+].[K+].C1COCC1>CC#N.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:31]=[C:30]([C:47]5[CH:46]=[CH:45][C:40]([C:41]([O:43][CH3:44])=[O:42])=[CH:39][C:38]=5[CH3:37])[CH:29]=[CH:28][C:27]=4[F:33])=[N:24][CH:23]=[CH:22][N:21]=3)[C@H:14]2[CH3:34])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 110870242-Methyl-4-methoxycarbonylphenylboronic acid, pinacol ester2×HCID 86627642HCID 86627642, compound

Product 1

HCID 86627643HCID 86627643, compound

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(5-chloro-2-fluorophenyl)pyrazin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (33 mg, 0.062 mmol), methyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (INTERMEDIATE 37, 14.39 mg, 0.052 mmol), 1,1′-bis(di-tert-butylphosphino) ferrocene palladium dichloride (6.30 mg, 9.27 mmol), K2CO3 (0.155 mL, 0.309 mmol) and THF (1 mL) were sealed in a microwave vessel and subjected to microwave irradiation at 140° C. for 20 min. LCMS of aliquot indicated about 40% conversion. Microwave heating was resumed at 140° C. for an additional 30 min. LCMS of the aliquot indicated about 10% of remaining unreacted starting material. Microwave heating was resumed for an additional 12 min at 140° C. The resulting crude material was diluted with MeCN and filtered. The filtrate was purified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min, 20 mL/min) to give a brown glass. The brown glass was further purified by preparative TLC (SiO2, 30% EtOAc/hexanes) to afford a colorless glass as the titled compound. LCMS calc.=647.17; found=648.38 (M+H)+.

Workup

  1. customirradiation at 140° C. for 20 min
  2. temperatureMicrowave heating
  3. temperatureMicrowave heating
  4. waitwas resumed for an additional 12 min at 140° C
  5. filtrationfiltered
  6. customThe filtrate was purified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
  7. washeluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min, 20 mL/min)
  8. customto give a brown glass
  9. customThe brown glass was further purified by preparative TLC (SiO2, 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0caf1cab4b5e4d979d3bbbb75a3dd251
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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