Acetic Acid → 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid

HRID 1396867Notes

Reaction equation

HRID 1396867 reaction equation
[NH:1]1[CH:5]([C:6]([OH:8])=[O:7])[CH2:4][CH:3]=[N:2]1.CCN(C(C)C)C(C)C.[CH:18]1([CH2:23][C@@H:24]([C:33](F)=[O:34])[CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21][CH2:20][CH2:19]1.C(O)(=O)C.[Cl-].[NH4+]>ClCCl>[CH:18]1([CH2:23][C@H:24]([CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:33]([N:1]2[CH:5]([C:6]([OH:8])=[O:7])[CH2:4][CH:3]=[N:2]2)=[O:34])[CH2:19][CH2:20][CH2:21][CH2:22]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 128798564,5-dihydro-1H-pyrazole-5-carboxylic acidHCID 86706344HCID 86706344, compound

Product 1

HCID 682877191-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acidYield 57.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4,5-dihydro-1H-pyrazole-5-carboxylic acid (1.44 g, 8.8 mmol) in dichloromethane (DCM) (62 ml) at 0° C. was added Hunig's base (9.25 ml, 53.0 mmol) followed by 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-fluoro-4-oxobutanoate (3.8 g, 8.8 mmol) in 10 mL DCM. The resulting mixture was allowed to warm to room temperature and stirred for 4 hours. The mixture was then cooled to 0° C. and acetic acid (2.5 ml, 44.1 mmol) was added, followed by sat. aq ammonium chloride (15 mL). The phases were separated and the aqueous phase was extracted once with DCM (20 mL). The combined organics were washed with brine (15 mL), dried over sodium sulfate, and concentrated to yield a yellow oil. This crude product was purified by Combiflash automated silica gel chromatography (0-100% EtOAc in hex) to afford 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (1.78 g, 5.05 mmol, 57% yield) as a clear oil. MS: 353 ([M+H]+).

Workup

  1. temperatureThe mixture was then cooled to 0° C.
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted once with DCM (20 mL)
  4. washThe combined organics were washed with brine (15 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customto yield a yellow oil
  8. customThis crude product was purified by Combiflash automated silica gel chromatography (0-100% EtOAc in hex)

Sources & evidence

ORD record
ord-f6aa37e15d644bd398c37bafaa32fae1
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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