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

HRID 472868Notes

Reaction equation

HRID 472868 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:29]=[C:11]3[N:12]=[C:13]([CH3:28])[C:14]([C@H:22]([OH:27])[C:23]([O:25][CH3:26])=[O:24])=[C:15]([CH:16]4[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(O[C:34]([CH3:37])([CH3:36])[CH3:35])(=O)C.Cl(O)(=O)(=O)=O>C(Cl)Cl.CCOCC>[C:34]([O:27][C@@H:22]([C:14]1[C:13]([CH3:28])=[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:29]=2)[C:15]=1[CH:16]1[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1)[C:23]([O:25][CH3:26])=[O:24])([CH3:37])([CH3:36])[CH3:35]

Participants

6

Reactant 3

HCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 66692981(S)-methyl 2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Product 1

HCID 66693715(S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 63.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-methyl 2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (0.067 g, 0.162 mmol) and tert-butyl acetate (1 ml, 7.40 mmol) in CH2Cl2 (3 mL) was added 70% perchloric acid (0.042 ml, 0.486 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-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (0.0481 g, 0.102 mmol, 63.2% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ: 7.96 (t, J=1.5 Hz, 1H), 7.87 (dt, J=7.6, 1.3 Hz, 1H), 7.41-7.31 (m, 2H), 6.75 (s, 1H), 5.40 (s, 1H), 3.87-3.77 (m, 1H), 3.70 (s, 3H), 2.93-2.79 (m, 2H), 2.73 (s, 3H), 1.96-1.85 (m, 2H), 1.77-1.68 (m, 2H), 1.54-1.38 (m, 4H), 1.25 (s, 9H). LCMS (M+H) calcd for C26H33ClN3O3: 470.22. found: 472.4.

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-a42f1a82eb6845eda2886506f432def4
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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