tert-Butyl acetate → (S)-ethyl 2-(tert-butoxy)-2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 472883

Reaction equation

HRID 472883 reaction equation
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=3)[C:10]([CH3:11])=[C:6]2[N:5]=[C:4]([CH3:19])[C:3]=1[C@H:20]([OH:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22].C(O[C:31]([CH3:34])([CH3:33])[CH3:32])(=O)C.Cl(O)(=O)(=O)=O>C(Cl)Cl>[C:31]([O:26][C@@H:20]([C:3]1[C:4]([CH3:19])=[N:5][C:6]2[N:7]([N:8]=[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=3)[C:10]=2[CH3:11])[C:2]=1[Cl:1])[C:21]([O:23][CH2:24][CH3:25])=[O:22])([CH3:34])([CH3:33])[CH3:32]

Participants

5

Reactant 3

HCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 86670293(S)-ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Product 1

HCID 86670294(S)-ethyl 2-(tert-butoxy)-2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 56.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (S)-ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (3.08 g, 7.81 mmol) in CH2Cl2 (130 ml) was treated with tert-butyl acetate (73.9 ml, 547 mmol) and perchloric acid (2.014 ml, 23.44 mmol), and the reaction was stoppered. The reaction was stirred for 2.5 hrs, then diluted with CH2Cl2 (130 ml) and carefully quenched with sat. NaHCO3 (100 mL). The organic layer was separated and washed with brine (100 mL), dried (Na2SO4), filtered and concentrated to give a light amber mobile oil. The crude product was purified by flash silica gel column chromatography, eluting with 10%-30% EtOAc in hexanes, to afford the product, (S)-ethyl 2-(tert-butoxy)-2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (2.05 g, 4.42 mmol, 56.5% yield) as a viscous oil, which began to crystallize upon standing. 1H NMR (500 MHz, CDCl3) δ: 7.87 (t, J=1.5 Hz, 1H), 7.74 (dt, J=7.3, 1.5 Hz, 1H), 7.46-7.36 (m, 2H), 5.63 (s, 1H), 4.19 (q, J=7.0 Hz, 2H), 2.68 (s, 3H), 2.51 (s, 3H), 1.26 (s, 9H), 1.21 (t, J=7.0 Hz, 3H).

Workup

  1. customcarefully quenched with sat. NaHCO3 (100 mL)
  2. customThe organic layer was separated
  3. washwashed with brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a light amber mobile oil
  8. customThe crude product was purified by flash silica gel column chromatography
  9. washeluting with 10%-30% EtOAc in hexanes

Sources & evidence

ORD record
ord-1bbe6e907cdb45b2a00d8b2af05a970e
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Linked notes

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