Benzyl Chloride → (S)-4-tert-Butoxycarbonylamino-5-methyl-hexanoic acid, benzyl ester

HRID 390209Notes

Reaction equation

HRID 390209 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:15]([CH3:17])[CH3:16])[CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:24](Cl)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)(O)[O-].[Na+]>CCCCCCC.ClCCl.O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:15]([CH3:17])[CH3:16])[CH2:10][CH2:11][C:12]([O:14][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 7503Benzyl ChlorideHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 57678353(4S)-4-{[(tert-butoxy)carbonyl]amino}-5-methylhexanoic acid

Product 1

HCID 58625169(S)-4-tert-Butoxycarbonylamino-5-methyl-hexanoic acid, benzyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21907733Dichloromethane heptaneSolvent

Procedure

A 50 mL, one-neck round bottom flask (equipped with a magnetic stirrer and a nitrogen inlet) was charged with (S)-4-tert-butoxycarbonylamino-5-methyl-hexanoic acid prepared as in Example 63 above (500 mg, 2.04 mmol), cesium carbonate (1.99 g, 6.11 mmol), benzyl chloride (773 mg, 6.11 mmol), and tetrahydrofuran (15 mL). The reaction was stirred at room temperature for three days (weekend) and then was heated to a mild reflux for 6 h. The reaction mixture was poured into saturated aqueous sodium bicarbonate (100 mL) and extracted with ethyl ether (2×100 mL). The combined organics were dried and concentrated to give 1 g of crude product. The residue was dissolved in heptane-dichloromethane (9:1, ˜7 mL) and eluted through a 12 g Isco silica gel cartridge to yield the title compound as a solid.

Workup

  1. customA 50 mL, one-neck round bottom flask (equipped with a magnetic stirrer and a nitrogen inlet)
  2. temperaturewas heated to
  3. temperaturea mild reflux for 6 h
  4. extractionextracted with ethyl ether (2×100 mL)
  5. customThe combined organics were dried
  6. concentrationconcentrated
  7. customto give 1 g of crude product
  8. washeluted through a 12 g Isco silica gel cartridge

Sources & evidence

ORD record
ord-77f66f7a4f8742cb931b1ff348f18539
Source dataset
uspto-grants-2013_02
Patent number
US08383637B2

Reaction notes

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