Hydrochloric Acid → 3-[(4-{[(4-Acetyl-3-hydroxy-2-methyl-phenyl)-methyl-amino]-methyl}-phenyl)-hydroxy-methyl]-benzonitrile

HRID 1818479Notes

Reaction equation

HRID 1818479 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]([OH:27])[C:19]3[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=3)[C:22]#[N:23])=[CH:14][CH:13]=2)=[C:6]([CH3:28])[C:5]=1[OH:29])(=[O:3])[CH3:2].C=O.[BH3-][C:33]#N.[Na+].Cl>C(#N)C>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([CH:18]([OH:27])[C:19]3[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=3)[C:22]#[N:23])=[CH:16][CH:17]=2)[CH3:33])=[C:6]([CH3:28])[C:5]=1[OH:29])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 666995203-({4-[(4-Acetyl-3-hydroxy-2-methyl-phenylamino)-methyl]-phenyl}-hydroxy-methyl)-benzonitrile

Product 1

HCID 666995023-[(4-{[(4-Acetyl-3-hydroxy-2-methyl-phenyl)-methyl-amino]-methyl}-phenyl)-hydroxy-methyl]-benzonitrileYield 94%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 3-({4-[(4-acetyl-3-hydroxy-2-methyl-phenylamino)-methyl]-phenyl}-hydroxy-methyl)-benzonitrile (138 mg, 0.36 mmol) in acetonitrile (14 mL) are added 37% aqueous solution of formaldehyde (140 μL) and NaCNBH3 (69 mg, 1.1 mmol). The pH of the mixture is adjusted to approximately 2 by dropwise addition of 1 N HCl over a 15 min period. The reaction was complete after 1.5 h, during which time the pH of the reaction mixture is monitored every 15 min using pH paper and kept at around 2 by addition of 1N HCl. The reaction mixture is quenched into H2O and basified with saturated aqueous NaHCO3. The mixture is extracted with EtOAc (3×), washed with brine, dried over Na2SO4, and concentrated. Obtained is the title compound as a yellow oil (135 mg, 94%). LC-MS (m/e): 399 (M−1).

Workup

  1. waitthe pH of the reaction mixture is monitored every 15 min
  2. customThe reaction mixture is quenched into H2O
  3. extractionThe mixture is extracted with EtOAc (3×)
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customObtained

Sources & evidence

ORD record
ord-031dcb28a3e94524a339cefee260e9c8
Source dataset
uspto-grants-2009_10
Patent number
US07598423B2

Reaction notes

Loading…