Isopropyl Acetate → (4-{[4-(Fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid

HRID 473896Notes

Reaction equation

HRID 473896 reaction equation
Cl.[O:2]1[C:8]2[CH:9]=[CH:10][C:11]([B:13]([OH:15])[OH:14])=[CH:12][C:7]=2[CH2:6][NH:5][CH2:4][CH2:3]1.C(=O)(O)[O-].[Na+].[F:21][CH2:22][CH:23]1[CH2:28][CH2:27][N:26]([C:29](Cl)=[O:30])[CH2:25][CH2:24]1.C(OC(C)C)(=O)C>C1COCC1>[F:21][CH2:22][CH:23]1[CH2:28][CH2:27][N:26]([C:29]([N:5]2[CH2:6][C:7]3[CH:12]=[C:11]([B:13]([OH:15])[OH:14])[CH:10]=[CH:9][C:8]=3[O:2][CH2:3][CH2:4]2)=[O:30])[CH2:25][CH2:24]1

Participants

6

Reactant 4

HCID 7915Isopropyl AcetateHCID 516892Sodium BicarbonateHCID 66820605(2,3,4,5-Tetrahydrobenzo[f][1,4]oxazepin-7-yl)boronic acid hydrochlorideHCID 866720264-(Fluoromethyl)piperidine-1-carbonyl chloride

Product 1

HCID 67514561(4-{[4-(Fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acidYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2,3,4,5-tetrahydro-1,4-benzoxazepin-7-ylboronic acid hydrochloride salt (188 mg, 0.82 mmol) was taken into 50% aqueous THF (2 mL) followed by addition of solid sodium bicarbonate (360 mg, 4.3 mmol) then 4-(fluoromethyl)piperidine-1-carbonyl chloride (reagent preparation 37) (218 mg, 1.21 mmol) in a minimum of THF. The mixture was stirred at room temperature over 1 h then partitioned with 0.5M aqueous hydrochloric acid and ethyl acetate. The organic solution was then brine washed, dried over anhydrous sodium sulfate, filtered and concentrated. The residue obtained was taken into isopropyl acetate and extracted once with 1M aqueous sodium hydroxide. The aqueous solution was then acidified to pH 2 using concentrated hydrochloric acid and extracted once with ethyl acetate then brine washed, dried over anhydrous sodium sulfate, filtered and concentrated to provide (4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (143 mg, 52% yield) as an amorphous residue. MS (EI) for C16H22BrFN2O4: 337 (MH+).

Workup

  1. customthen partitioned with 0.5M aqueous hydrochloric acid and ethyl acetate
  2. washbrine washed
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue obtained
  7. extractionextracted once with 1M aqueous sodium hydroxide
  8. extractionextracted once with ethyl acetate
  9. washbrine washed
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-f1b261545802427c89a0fa664261c838
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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