Hydrochloric Acid → Tert-butyl 5-biphenyl-4-yl-3-oxopentanoate

HRID 1297253Notes

Reaction equation

HRID 1297253 reaction equation
[C:1]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[C:19]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:24]=[CH:23][C:22]([CH:25](C(O)CC)C(O)=O)=[CH:21][CH:20]=1.Cl>O1CCCC1>[C:8]([O:7][C:1](=[O:6])[CH2:2][C:3](=[O:4])[CH2:5][CH2:25][C:22]1[CH:23]=[CH:24][C:19]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[CH:20][CH:21]=1)([CH3:11])([CH3:10])[CH3:9]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 15538Tert-butyl acetoacetateHCID 24758Sodium hydrideHCID 13108284Biphenyl-4-yl-3-hydroxy-pentanoic acid2×HCID 178418339Butyllithium

Product 1

HCID 58914664Tert-butyl 5-biphenyl-4-yl-3-oxopentanoateYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of t-butyl acetoaceate (1.84 mL, 11.1 mmol) in tetrahydrofuran (20 mL) was added to a stirred suspension of sodium hydride (488 mg, 12.2 mmol) in tetrahydrofuran (10 mL) at 0° C. under nitrogen. After stirring for 10 minutes n-butyl lithium (1.6 M in hexanes; 7.3 mL, 11.6 mmol) was added dropwise over 2 minutes then stirring was continued for a further 10 minutes. A solution of 4-bromomethyl-biphenyl (Intermediate 1, 3.00 g, 12.2 mmol) in tetrahydrofuran (6 mL) was added dropwise over 10 minutes and the resulting solution stirred at 0° C. for 1.5 hours. 6 M Hydrochloric acid (15 mL) was added then the crude reaction mixture was extracted with diethyl ether (3×50 mL). The organic phases were combined, washed with brine (50 mL), dried (MgSO4) then the solvent evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (1:20 diethyl ether:cyclohexane) to give the title compound (1.37 g, 38%) as a yellow solid. LC/MS: 3.78 min; z/e 342, calcd (M+NH4) 342. 1H NMR (400 MHz: CDCl3): 7.55 (2 H), 7.50 (2 H), 7.43 (2 H), 7.32 (1 H), 7.25 (2 H), 3.34 (2 H), 2.95 (4 H), 1.45 (9 H).

Workup

  1. additionwas added dropwise over 2 minutes
  2. stirringthe resulting solution stirred at 0° C. for 1.5 hours
  3. customthe crude reaction mixture
  4. extractionwas extracted with diethyl ether (3×50 mL)
  5. washwashed with brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. customthe solvent evaporated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel (1:20 diethyl ether:cyclohexane)

Sources & evidence

ORD record
ord-8357292bb0d64c71961d9127f4cbcaa8
Source dataset
uspto-grants-2007_07
Patent number
US07250439B2

Reaction notes

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