2,6-Lutidine → (S)-4-(2-bromo-1-(tert-butyldimethylsilyloxy)ethyl)benzonitrile

HRID 1948495Notes

Reaction equation

HRID 1948495 reaction equation
[Br:1][CH2:2][C@H:3]([C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][CH:6]=1)[OH:4].CC1C=CC=C(C)N=1.[Si:21](OS(C(F)(F)F)(=O)=O)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]>C(Cl)Cl.C(OCC)(=O)C>[Br:1][CH2:2][C@H:3]([C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][CH:6]=1)[O:4][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 66955119(S)-4-(2-bromo-1-hydroxyethyl)benzonitrile

Product 1

HCID 66955431(S)-4-(2-bromo-1-(tert-butyldimethylsilyloxy)ethyl)benzonitrileYield 115.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (S)-4-(2-bromo-1-hydroxyethyl)benzonitrile (6.9 g, 30.5 mmol) and 2,6-dimethylpyridine (7.82 mL, 67.1 mmol) in DCM (20 mL) was added t-butyl-dimethylsilyltrifluoromethanesulfonate (14.02 mL, 61.0 mmol). The reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed with saturated NaCl. The organic layer was dried MgSO4, filtered and concentrated. The crude material was purified on a 80 gram silica column and eluting with an EtOAc/Hex gradient to afford 12 g of (S)-4-(2-bromo-1-(tert-butyldimethylsilyloxy)ethyl)benzonitrile. MS (M+1)=340/342. HPLC Peak RT=2.16 minutes. 1H NMR (400 MHz, CDCl3) δ ppm 7.65 (2H, d), 7.45 (2H, d), 4.88 (1H, dd), 3.42 (1H, q), 3.39 (1H, dd), 0.85 (9H, s), 0.12 (3H, s), −0.09 (3H, s).

Workup

  1. washwashed with saturated NaCl
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customThe crude material was purified on a 80 gram silica column
  5. washeluting with an EtOAc/Hex gradient

Sources & evidence

ORD record
ord-8abf08f4b5074a09b24362d3ebe14aa7
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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