Pyridine → N-(3,5-bis(hydroxymethyl)phenyl)-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-4-methyl-4-(methyldisulfanyl)pentanamide

HRID 2403524Notes

Reaction equation

HRID 2403524 reaction equation
[Si]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([N:25]([CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH3:45])[C:26](=[O:35])[CH2:27][CH2:28][C:29]([CH3:34])([S:31][S:32][CH3:33])[CH3:30])[CH:13]=[C:14]([CH2:16][O:17][Si](C(C)(C)C)(C)C)[CH:15]=1)(C(C)(C)C)(C)C.N1C=CC=CC=1>C(#N)C.C(OCC)(=O)C>[OH:8][CH2:9][C:10]1[CH:11]=[C:12]([N:25]([CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH3:45])[C:26](=[O:35])[CH2:27][CH2:28][C:29]([CH3:34])([S:31][S:32][CH3:33])[CH3:30])[CH:13]=[C:14]([CH2:16][OH:17])[CH:15]=1

Participants

5

Reactant 2

HCID 1049Pyridine2×HCID 59440082N-(3,5-bis((tert-butyldimethylsilyloxy)methyl)phenyl)-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-4-methyl-4-(methyldisulfanyl)pentanamide

Product 1

HCID 59440211N-(3,5-bis(hydroxymethyl)phenyl)-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-4-methyl-4-(methyldisulfanyl)pentanamideYield 89.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of N-(3,5-bis((tert-butyldimethylsilyloxy)methyl)phenyl)-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-4-methyl-4-(methyldisulfanyl)pentanamide (267b) (315 mg, 0.447 mmol) in anhydrous acetonitrile (7.0 mL) at 0° C. was added anhydrous pyridine (7.00 mL) followed by dropwise addition of HF.Pyridine (3.1 mL, 1 mL/100 mg). The reaction stirred at 0° C. for two hours. It was diluted with ethyl acetate and slowly quenched with saturated sodium bicarbonate. The mixture was extracted three times with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography, eluting with 5% MeOH/CH2Cl2, yielded N-(3,5-bis(hydroxymethyl)phenyl)-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-4-methyl-4-(methyldisulfanyl)pentanamide (267c) (190 mg, 89%). 1H NMR (400 Hz, CDCl3): δ 7.21 (s, 1H), 7.16 (s, 2H), 4.63 (s, 4H), 3.79 (t, J=5.2, 5.6 Hz, 2H), 3.53 (m, 6H), 3.48 (m, 4H), 3.29 (s, 3H), 2.53 (s, 2H), 2.27 (s, 3H), 2.07 (m, 2H), 1.84 (m, 2H), 1.08 (s, 6H); MS (m/z). found 498.2 (M+Na)+.

Workup

  1. additionfollowed by dropwise addition of HF
  2. customslowly quenched with saturated sodium bicarbonate
  3. extractionThe mixture was extracted three times with ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography
  9. washeluting with 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-41b88e2f3bfc4cf395295ddcb2f8332d
Source dataset
uspto-grants-2014_08
Patent number
US08802667B2

Reaction notes

Loading…