Hydrochloric Acid → HCID 67332127, compound

HRID 1672252Notes

Reaction equation

HRID 1672252 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH2:4][CH2:5][CH:6]([NH:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:15][CH:14]=1)=[O:12])[C:7](O)=[O:8].CCN(CC)CC.ClC(OCC)=O.[BH4-].[Na+].Cl>C1COCC1.CO>[CH3:1][O:2][C:3](=[O:25])[CH2:4][CH2:5][CH:6]([NH:10][C:11]([C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:17][CH:18]=1)=[O:12])[CH2:7][OH:8]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 45496562HCID 45496562, compound

Product 1

HCID 67332127HCID 67332127, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

2-[(Biphenyl-4-carbonyl)-amino]-pentanedioic acid 5-methyl ester (1.128 g, 3.30 mmol, 1.0 equiv.) was dissolved in THF (35 mL). The mixture was cooled to −20° C., followed by the addition of Et3N (343 mg, 3.3 mmol, 1.0 equiv.) and ethyl chloroformate (358 mg, 3.3 mmol, 1.0 equiv.). After stirring for 20 minutes, NaBH4 (375 mg, 9.9 mmol, 3 equiv.) was added and the temperature was raised to −10° C. After stirring for 5 min, MeOH (30 mL) was introduced and the mixture was further stirred for 20 min at this temperature and then at 0° C. for 20 min. 1N HCl was then added slowly to quench the reaction. Solvent was evaporated and the residue partitioned between EtOAc and H2O. The organic layer was washed with brine, dried over MgSO4, and removed solvent by rotavap. The crude mixture was then purified by column chromatography (silica gel, 3% MeOH/CH2Cl2) to afford 333 mg of 4-[(Biphenyl-4-carbonyl)-amino]-5-hydroxy-pentanoic acid methyl ester in 31% yield. MS (ESI) m/z 328.

Workup

  1. temperaturethe temperature was raised to −10° C
  2. stirringAfter stirring for 5 min
  3. stirringthe mixture was further stirred for 20 min at this temperature
  4. waitat 0° C. for 20 min
  5. customto quench
  6. customthe reaction
  7. customSolvent was evaporated
  8. customthe residue partitioned between EtOAc and H2O
  9. washThe organic layer was washed with brine
  10. dry with materialdried over MgSO4
  11. customremoved solvent by rotavap
  12. customThe crude mixture was then purified by column chromatography (silica gel, 3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-5294b7280fa54f158e30c2169eb1d9db
Source dataset
uspto-grants-2011_08
Patent number
US07998965B2

Reaction notes

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