Aniline → (R)-2-(tert-butyldiphenylsilyloxy)-4-hydroxy-N-phenylbutanamide

HRID 2261475Notes

Reaction equation

HRID 2261475 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Al](C)C.[Si:12]([O:29][C@@H:30]1[CH2:34][CH2:33][O:32][C:31]1=[O:35])([C:25]([CH3:28])([CH3:27])[CH3:26])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(O)(=O)C(C(C(O)=O)O)O.[K].[Na]>C(Cl)Cl>[Si:12]([O:29][C@H:30]([CH2:34][CH2:33][OH:32])[C:31]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:35])([C:25]([CH3:28])([CH3:27])[CH3:26])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 6115AnilineHCID 16682925TrimethylaluminumHCID 53797635(R)-3-(tert-butyldiphenylsilyloxy)dihydrofuran-2(3H)-oneHCID 86590012HCID 86590012, compound

Product 1

HCID 59593434(R)-2-(tert-butyldiphenylsilyloxy)-4-hydroxy-N-phenylbutanamideYield 78.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of aniline (356 mg, 348 μL, 3.82 mmol) in DCM (17 mL) was added trimethylaluminum (2.0M, 2.1 mL, 4.2 mmol) dropwise and the reaction mixture was stirred at RT for 40 min. A solution of (R)-3-(tert-butyldiphenylsilyloxy)-dihydrofuran-2(3H)-one (1.00 g, 2.94 mmol) in DCM (12 mL) was added dropwise and the reaction mixture was stirred at RT for 16 hours. The reaction mixture was poured into a saturated solution of sodium potassium tartaric acid and stirred for 15 min. The layers were separated, and the aqueous layer was washed with DCM (4×). The combined organics were washed with 0.1M HCl (2×), brine, dried over Na2SO4 and evaporated to dryness. Purification by silica gel chromatography (10-30% EtOAc in hexane) afforded the (R)-2-(tert-butyldiphenylsilyloxy)-4-hydroxy-N-phenylbutanamide (1.00 g, 78%). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=434.7; tR=2.16 min.

Workup

  1. stirringthe reaction mixture was stirred at RT for 16 hours
  2. stirringstirred for 15 min
  3. customThe layers were separated
  4. washthe aqueous layer was washed with DCM (4×)
  5. washThe combined organics were washed with 0.1M HCl (2×), brine
  6. dry with materialdried over Na2SO4
  7. customevaporated to dryness
  8. customPurification by silica gel chromatography (10-30% EtOAc in hexane)

Sources & evidence

ORD record
ord-db596d7a6dc24b17bd3c34c7f7d32c72
Source dataset
uspto-grants-2010_12
Patent number
US07846954B2

Reaction notes

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