Hydrochloric Acid → HCID 178457438, compound

HRID 2169306Notes

Reaction equation

HRID 2169306 reaction equation
[Si]([O:8][CH2:9][CH2:10][N:11]([CH:46]([CH3:48])[CH3:47])[C:12]([C:14]1[C:19]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:18]([OH:28])[N:17]=[C:16]([CH2:29][C:30]2([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:39][CH2:38][C:33]3(OCC[O:34]3)[CH2:32][CH2:31]2)[N:15]=1)=[O:13])(C(C)(C)C)(C)C.Cl.C(OCC)(=O)C>O1CCCC1>[OH:8][CH2:9][CH2:10][N:11]([CH:46]([CH3:48])[CH3:47])[C:12]([C:14]1[C:19]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:18]([OH:28])[N:17]=[C:16]([CH2:29][C:30]2([C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)[CH2:31][CH2:32][C:33](=[O:34])[CH2:38][CH2:39]2)[N:15]=1)=[O:13]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 178457473HCID 178457473, compound

Product 1

HCID 178457438HCID 178457438, compoundYield 66.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-benzyloxy-6-hydroxy-2-(8-phenyl-1,4-dioxa-spiro[4.5]dec-8-ylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (271) (500 mg, 0.74 mmol) in tetrahydrofuran (30.0 mL) was added 2.1N aqueous HCl (6.0 mL) and stirred at room temperature for 7 h while silica thin layer chromatography was performed (only ethyl acetate; Rf=0.25). The reaction mixture was concentrated in vacuum and diluted with ethyl acetate (50 mL), washed with aqueous NaHCO3 solution (20 mL) and brine (30 mL) and dried and concentrated in vacuum to get a crude mass which was purified by CombiFlash using a gradient eluent mixture of methanol and dichloromethane to get pure 5-benzyloxy-6-hydroxy-2-(4-oxo-1-phenyl-cyclohexylmethyl)-pyrimidine-4-carboxylic acid (2-hydroxyethyl)-isopropylamide (272) (255 mg, 66.6%) as a white sticky solid.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuum
  2. additiondiluted with ethyl acetate (50 mL)
  3. washwashed with aqueous NaHCO3 solution (20 mL) and brine (30 mL)
  4. customdried
  5. concentrationconcentrated in vacuum
  6. customto get a crude mass which
  7. customwas purified by CombiFlash
  8. additiona gradient eluent mixture of methanol and dichloromethane

Sources & evidence

ORD record
ord-b8c3d8f9420d4dd7bcbec39551e9e3f1
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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