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

HRID 2088776Notes

Reaction equation

HRID 2088776 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-e98f31ee66c8470789d7f86a7391d9af
Source dataset
uspto-grants-2013_05
Patent number
US08436006B2

Reaction notes

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