Sodium Bicarbonate → HCID 59668695, compound

HRID 237933Notes

Reaction equation

HRID 237933 reaction equation
O[C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]2[NH:15][C:16]([C:19]3[CH:24]=[CH:23][C:22]([B:25]4[O:29]C(C)(C)C(C)(C)[O:26]4)=[CH:21][CH:20]=3)=[CH:17][N:18]=2)[CH2:3]1.COCCN(S(F)(F)[F:44])CCOC.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:10]([O:9][C:7]([N:5]1[CH2:6][C@@H:2]([F:44])[CH2:3][C@H:4]1[C:14]1[NH:15][C:16]([C:19]2[CH:24]=[CH:23][C:22]([B:25]([OH:29])[OH:26])=[CH:21][CH:20]=2)=[CH:17][N:18]=1)=[O:8])([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 59166497HCID 59166497, compound

Product 1

HCID 59668695HCID 59668695, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

(2S,4R)-tert-butyl 4-hydroxy-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate, 1-2c (1.5 g, 3.3 mmol) was added as a solid to a solution of bis(2-methoxyethyl)aminosulfur trifluoride (0.91 mL, 5.0 mmol) in 15 mL CH2Cl2 cooled to −78° C. Reaction was stirred at −78° C. for two hours and then warmed to room temperature and stirred for 2 hours. Reaction was poured into saturated sodium bicarbonate solution and stirred until bubbling ceased. Layers were separated and aqueous layer washed one time with CH2Cl2. Combined organics were washed with brine, dried (MgSO4), filtered, and concentrated to give a brown oil. The oil was chromatographed on silica gel with 5% MeOH/CH2Cl2 to yield 4-(2-((2S,4S)-1-(tert-butoxycarbonyl)-4-fluoropyrrolidin-2-yl)-1H-imidazol-5-yl)phenylboronic acid as a tan solid (0.46 g, 37%). LCMS—Luna C-18 3.0×50 mm, 0 to 100% B over 4.0 minute gradient, 1 minute hold time, A=5% acetonitrile, 95% water, 10 mm ammonium acetate, B=95% acetonitrile, 5% water, 10 mm ammonium acetate, tR=1.46 min, Anal. Calcd. for C18H23B1F1N3O4 375.18. found 376.12 (M+H)+ JG-22 is synthesized from JG-20 and JG-21 as described in Example 28 step c.

Workup

  1. customReaction
  2. temperaturewarmed to room temperature
  3. stirringstirred for 2 hours
  4. customReaction
  5. stirringstirred
  6. customuntil bubbling
  7. customLayers were separated
  8. washaqueous layer washed one time with CH2Cl2
  9. washCombined organics were washed with brine
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a brown oil
  14. customThe oil was chromatographed on silica gel with 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-384839a44ab54c3b9b904bd35dc5ebc4
Source dataset
uspto-grants-2014_02
Patent number
US08642025B2

Reaction notes

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