2-Hydroxyisobutyric acid → HCID 68914301, compound

HRID 732720Notes

Reaction equation

HRID 732720 reaction equation
[OH:1][C:2]([CH3:7])([CH3:6])[C:3](O)=[O:4].CCN=C=NCCCN(C)C.[ClH:19].C1C=CC2N(O)N=NC=2C=1.[C:30]1([C@H:40]([N:42]([CH2:50][CH:51]2[CH:55]([C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)[CH2:54][NH:53][CH2:52]2)C(=O)OC(C)(C)C)[CH3:41])[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:33]=[CH:32][CH:31]=1.C(=O)(O)[O-].[Na+]>O.C(#N)C>[ClH:19].[CH3:6][C:2]([OH:1])([CH3:7])[C:3]([N:53]1[CH2:54][CH:55]([C:56]2[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=2)[CH:51]([CH2:50][NH:42][C@@H:40]([C:30]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:33]=[CH:32][CH:31]=2)[CH3:41])[CH2:52]1)=[O:4]

Participants

8

Reactant 5

HCID 116712-Hydroxyisobutyric acidHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86628564HCID 86628564, compound

Product 1

HCID 68914301HCID 68914301, compoundYield 10.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

An 8 ml acetonitrile solution of 192 mg of 2-hydroxy-2-methylpropanoic acid was mixed with 392 mg of WSC hydrochloride, 62 mg of HOBt and 400 mg of tert-butyl [(1R)-1-(1-naphthyl)ethyl]{[4-phenylpyrrolidin-3-yl]methyl}carbamate and stirred at 60° C. for 12 hours. After completion of the reaction, 30 ml of water was added thereto, and acetonitrile was evaporated. This was extracted with ethylamine, the organic layer was concentrated, and then the thus obtained residue was purified by a silica gel column chromatography (chloroform-ethyl acetate). This was further mixed with 2 ml of ethyl acetate and 0.5 ml of 4 M hydrogen chloride/ethyl acetate and stirred at 60° C. for 4 hours. After completion of the reaction, this was neutralized with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate and concentrated, and then the thus obtained residue was again purified by a silica gel column chromatography (chloroform-ethyl acetate), treated with 4 M hydrogen chloride/ethyl acetate and crystallized (ethyl acetate-hexane) to obtain 43 mg of 2-methyl-1-[3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]-1-oxopropan-2-ol hydrochloride as a colorless solid

Workup

  1. additionwas added
  2. customacetonitrile was evaporated
  3. extractionThis was extracted with ethylamine
  4. concentrationthe organic layer was concentrated
  5. customthe thus obtained residue was purified by a silica gel column chromatography (chloroform-ethyl acetate)
  6. additionThis was further mixed with 2 ml of ethyl acetate and 0.5 ml of 4 M hydrogen chloride/ethyl acetate
  7. stirringstirred at 60° C. for 4 hours
  8. customAfter completion of the reaction
  9. extractionextracted with ethyl acetate
  10. concentrationconcentrated
  11. customthe thus obtained residue was again purified by a silica gel column chromatography (chloroform-ethyl acetate)
  12. additiontreated with 4 M hydrogen chloride/ethyl acetate
  13. customcrystallized (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-866c78994b9e432f8e2c3299c058b9f5
Source dataset
uspto-grants-2009_09
Patent number
US07585886B2

Reaction notes

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