M-Cresol → t-butyl (1S)-2-(benzyloxy)-1-[(3-methylphenoxy)methyl]ethylcarbamate

HRID 12402

Reaction equation

HRID 12402 reaction equation
[CH2:1]([O:8][CH2:9][C@H:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:11][OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(Cl)(=O)=O.[Cl-].[Li+].C(=O)([O-])[O-].[K+].[K+].[CH:34]1[C:39](O)=[CH:38][CH:37]=[CH:36][C:35]=1[CH3:41]>ClCCl.C(OCC)(=O)C.CN(C)C=O.C(N(CC)CC)C>[CH2:1]([O:8][CH2:9][C@H:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:19])[CH3:18])[CH2:11][O:12][C:39]1[CH:38]=[CH:37][CH:36]=[C:35]([CH3:41])[CH:34]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

10

Reactant 5

HCID 342M-CresolHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 433294Lithium ChlorideHCID 11065873(R)-(+)-3-Benzyloxy-2-(Boc-amino)-1-propanol

Product 1

HCID 86761116t-butyl (1S)-2-(benzyloxy)-1-[(3-methylphenoxy)methyl]ethylcarbamate

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To t-butyl (1R)-2-(benzyloxy)-1-(hydroxymethyl)ethylcarbamate (3.23 g) obtained in Step 1 were added dichloromethane (40 ml), methanesulfonyl chloride (1.07 ml) and triethylamine (3.20 ml), and the mixture was stirred at 0° C. for 3 hrs. The reaction mixture was diluted with dichloromethane and, after washing with water, the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated to give a crude product. To this crude product were added dimethylformamide (30 ml) and lithium chloride (2.4 g), and the mixture was stirred overnight at 40° C. The solvent was evaporated, and the residue was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated to give a crude product. To this crude product were added dimethylformamide (20 ml), potassium carbonate (2.4 g) and m-cresol (1.47 ml), and the mixture was stirred overnight at 90° C. The mixture was diluted with ethyl acetate and, after washing with water, the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained crude product was purified by silica gel chromatography (ethyl acetate-hexane) to give t-butyl (1S)-2-(benzyloxy)-1-[(3-methylphenoxy)methyl]ethylcarbamate (1.5 g).

Workup

  1. washafter washing with water
  2. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  3. customThe solvent was evaporated
  4. customto give a crude product
  5. stirringthe mixture was stirred overnight at 40° C
  6. customThe solvent was evaporated
  7. additionthe residue was diluted with ethyl acetate
  8. washwashed with water
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. customthe solvent was evaporated
  11. customto give a crude product
  12. stirringthe mixture was stirred overnight at 90° C
  13. washafter washing with water
  14. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  15. customThe solvent was evaporated
  16. customthe obtained crude product
  17. customwas purified by silica gel chromatography (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-a762014a54fb470d8dbdaa3e765d6a38
Source dataset
uspto-grants-2010_06
Patent number
US07728005B2

Linked notes

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