tert-Butyl acetate → (S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 472862Notes

Reaction equation

HRID 472862 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:30]=[C:11]3[N:12]=[C:13]([CH3:29])[C:14]([C@H:23]([OH:28])[C:24]([O:26][CH3:27])=[O:25])=[C:15]([C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(O[C:35]([CH3:38])([CH3:37])[CH3:36])(=O)C.Cl(O)(=O)(=O)=O>C(Cl)Cl.CCOCC>[C:35]([O:28][C@@H:23]([C:14]1[C:13]([CH3:29])=[N:12][C:11]2[N:10]([N:9]=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[CH:30]=2)[C:15]=1[C:16]1[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=1)[C:24]([O:26][CH3:27])=[O:25])([CH3:38])([CH3:37])[CH3:36]

Participants

6

Reactant 3

HCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 66692935(S)-methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Product 1

HCID 66693648(S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 70.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (0.06 g, 0.141 mmol) and tert-butyl acetate (0.952 ml, 7.04 mmol) in CH2Cl2 (3 mL) was added 70% perchloric acid (0.036 ml, 0.423 mmol) at rt. After 2 h, the reaction was diluted with Et2O (50 mL), washed with sat. Na2CO3 (2×5 mL), dried (Na2SO4), filtered and concentrated to give yellow solid which was purified by prep-HPLC to afford (S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (0.0478 g, 0.099 mmol, 70.4% yield) as while solid. 1H NMR (500 MHz, CDCl3) δ: 7.83 (s, 1H), 7.77-7.69 (m, 2H), 7.67-7.62 (m, 1H), 7.35-7.26 (m, 4H), 6.87 (s, 1H), 5.07 (s, 1H), 3.81 (s, 3H), 2.66 (s, 3H), 0.96 (s, 9H). LCMS (M+H) calcd for C26H26ClFN3O3: 482.16. found: 482.3.

Workup

  1. washwashed with sat. Na2CO3 (2×5 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give yellow solid which
  6. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-4d55c44bbff14ec191fd371aec49f45e
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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