Hydrochloric Acid → 4-((1-(tert-butoxycarbonyl)-4-isocyanatopiperidin-4-yl)methyl)-1-tert-butyl-1H-pyrazole-3-carboxylic acid

HRID 711039Notes

Reaction equation

HRID 711039 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[C:19]([C:27]([OH:29])=[O:28])=[N:20][N:21]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:22]=2)(C(=O)N)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:30](=[O:33])(O)[O-].[Na+].FC(F)(F)C(OC1C(OC(=O)C(F)(F)F)=C(I=O)C=CC=1)=O.Cl.C(#[N:60])C>O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([CH2:17][C:18]2[C:19]([C:27]([OH:29])=[O:28])=[N:20][N:21]([C:23]([CH3:25])([CH3:26])[CH3:24])[CH:22]=2)([N:60]=[C:30]=[O:33])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 516892Sodium BicarbonateHCID 22352379Bis(trifluoroacetoxy) iodosobenzeneHCID 674914864-((1-(tert-butoxycarbonyl)-4-carbamoylpiperidin-4-yl)methyl)-1-tert-butyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 866646154-((1-(tert-butoxycarbonyl)-4-isocyanatopiperidin-4-yl)methyl)-1-tert-butyl-1H-pyrazole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a suspension of 4-((1-(tert-butoxycarbonyl)-4-carbamoylpiperidin-4-yl)methyl)-1-tert-butyl-1H-pyrazole-3-carboxylic acid (388 mg, 0.95 mmol) in acetonitrile (20 mL) was added sodium bicarbonate (319 mg, 3.80 mmol) and bis(trifluoroacetoxy) iodosobenzene (632 mg, 1.42 mmol). The mixture was stirred 90 minutes at room temperature, diluted with 50 mL water, acidified with 1 N aqueous hydrochloric acid, and then extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The resulting residue was purified by flash chromatography (1-10% methanol/dichloromethane, 25 g silica gel) to yield 4-((1-(tert-butoxycarbonyl)-4-isocyanatopiperidin-4-yl)methyl)-1-tert-butyl-1H-pyrazole-3-carboxylic acid (172 mg) as a colorless solid. −APCI (M−H) 405.4; 1H NMR (400 MHz, DMSO-d6, δ): 12.52 (br. s., 1H), 7.82 (s, 1H), 3.83 (br. s., 2H), 3.03 (s, 2H), 2.82 (br. s., 2H), 1.49 (m, 13H), 1.36 (m, 9H).

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. dry with materialThe combined organic extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was purified by flash chromatography (1-10% methanol/dichloromethane, 25 g silica gel)

Sources & evidence

ORD record
ord-783fdc8ec3f0448f99c859148b599693
Source dataset
uspto-grants-2015_11
Patent number
US09181252B2

Reaction notes

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