Hydrochloric Acid → HCID 136408093, compound

HRID 1480621Notes

Reaction equation

HRID 1480621 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[C:8]([OH:13])=[C:9]([CH:12]=1)[CH:10]=O)([CH3:4])([CH3:3])[CH3:2].[C:24]([NH2:28])([CH3:27])([CH3:26])[CH3:25].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[ClH:43]>CO>[ClH:43].[C:1]([C:5]1[CH:6]=[C:7]([C:14]2[N:19]=[C:18]([C:20]([F:21])([F:22])[F:23])[CH:17]=[CH:16][N:15]=2)[C:8]([OH:13])=[C:9]([CH2:10][NH:28][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:12]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6385Tert-ButylamineHCID 5049666Sodium triacetoxyborohydride3×HCID 136408092HCID 136408092, compound

Product 1

HCID 136408093HCID 136408093, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-(tert-butyl)-2-hydroxy-3-(4-(trifluoromethyl)pyrimidin-2-yl)benzaldehyde (324 mg, 1.00 mmol) and tert-butylamine (0.21 mL, 2.00 mmol) in methanol (10 mL) was added sodium triacetoxyborohydride (254 mg, 1.20 mmol). The solution was stirred at 25° C. for one hour at which time a second portion of sodium triacetoxyborohydride (254 mg, 1.20 mmol) was added. After one hour a third portion of sodium triacetoxyborohydride (254 mg, 1.20 mmol) was added and the mixture was stirred for one hour. The solution was brought to pH 1 by the addition of 1N solution of hydrochloric acid and then partitioned between ethyl acetate (25 mL) and saturated aqueous sodium bicarbonate solution (25 mL). The organic phase was separated, concentrated under reduced pressure and purified using flash chromatography on silica eluting with a solvent gradient of 100:0 to 0:100 v/v 100% dichloromethane to a solution of 10% methanol, 1% ammonium hydroxide, 89% dichloromethane. The product was further purified using flash chromatography on silica eluting with a solvent gradient of 0 to 100% acetone in hexanes. The residue was dissolved in an excess of a 1N solution of hydrochloric acid in ethanol, the solvent was removed under reduced pressure and the solid was triturated with ether to give 4-(tert-butyl)-2-((tert-butylamino)methyl)-6-(4-(trifluoromethyl)pyrimidin-2-yl)phenol hydrochloride (156 mg, 38% yield) as an off-white solid.

Workup

  1. additionwas added
  2. custompartitioned between ethyl acetate (25 mL) and saturated aqueous sodium bicarbonate solution (25 mL)
  3. customThe organic phase was separated
  4. concentrationconcentrated under reduced pressure
  5. custompurified
  6. customThe product was further purified
  7. dissolutionThe residue was dissolved in an excess of a 1N solution of hydrochloric acid in ethanol
  8. customthe solvent was removed under reduced pressure
  9. customthe solid was triturated with ether

Sources & evidence

ORD record
ord-264ec8e3ba0541b197b78aa553e3833a
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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