Hydrochloric Acid → HCID 178519972, compound

HRID 2169366Notes

Reaction equation

HRID 2169366 reaction equation
[Si]([O:8][CH2:9][CH2:10][N:11]([CH2:42][CH:43]1[CH2:45][CH2:44]1)[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:35]3[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=3)[CH2:34][CH2:33][CH2:32][CH2:31]2)[N:15]=1)=[O:13])(C(C)(C)C)(C)C.Cl.C(OCC)(=O)C>O1CCCC1>[CH:43]1([CH2:42][N:11]([CH2:10][CH2:9][OH:8])[C:12]([C:14]2[C:19]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:18]([OH:28])[N:17]=[C:16]([CH2:29][C:30]3([C:35]4[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=4)[CH2:34][CH2:33][CH2:32][CH2:31]3)[N:15]=2)=[O:13])[CH2:45][CH2:44]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 178455249HCID 178455249, compound

Product 1

HCID 178519972HCID 178519972, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5-benzyloxy-2-[1-(4-chlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-cyclopropylmethyl-amide (329) (580 mg, crude) in tetrahydrofuran (30 mL) was added 1N aq.HCl (6 mL) at room temperature and stirring was continued for 1 h (TLC; 100% ethyl acetate/UV/SiO2, Rf=0.2). Tetrahydrofuran was removed in vacuo and the crude mass was dissolved in ethyl acetate (50 mL) and washed with NaHCO3 solution (10 mL), water (20 mL) and brine (20 mL); The organic phase was dried and concentrated in vacuo to get a crude mass which was purified by CombiFlash using a gradient eluent mixture of ethyl acetate and hexane to get pure 5-benzyloxy-2-[1-(4-chlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid cyclopropylmethyl-(2-hydroxyethyl)-amide (330) (390 mg, 94% two steps) as an off-white sticky solid.

Workup

  1. customTetrahydrofuran was removed in vacuo
  2. dissolutionthe crude mass was dissolved in ethyl acetate (50 mL)
  3. washwashed with NaHCO3 solution (10 mL), water (20 mL) and brine (20 mL)
  4. customThe organic phase was dried
  5. concentrationconcentrated in vacuo
  6. customto get a crude mass which
  7. customwas purified by CombiFlash
  8. additiona gradient eluent mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-cf9718e89474471bb2f393af4d4fb578
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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