tert-Butyl acetate → (S)-methyl 2-(tert-butoxy)-2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 472876Notes

Reaction equation

HRID 472876 reaction equation
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[CH:12]=3)[CH:10]=[C:6]2[N:5]=[C:4]([CH3:21])[C:3]=1[C@H:22]([OH:27])[C:23]([O:25][CH3:26])=[O:24].C(O[C:32]([CH3:35])([CH3:34])[CH3:33])(=O)C.Cl(O)(=O)(=O)=O>C(Cl)Cl>[C:32]([O:27][C@@H:22]([C:3]1[C:4]([CH3:21])=[N:5][C:6]2[N:7]([N:8]=[C:9]([C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[CH:12]=3)[CH:10]=2)[C:2]=1[Cl:1])[C:23]([O:25][CH3:26])=[O:24])([CH3:35])([CH3:34])[CH3:33]

Participants

5

Reactant 3

HCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 86670288(S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Product 1

HCID 86670289(S)-methyl 2-(tert-butoxy)-2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 72.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (S)-methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (888 mg, 2.301 mmol) in CH2Cl2 (45 mL) and t-butyl acetate (21.76 mL, 161 mmol) at rt was added perchloric acid (0.593 mL, 6.90 mmol). After 2.5 h, the reaction mixture was diluted with CH2Cl2 (50 mL), carefully quenched with sat. NaHCO3 (50 mL), organic layer separated and washed with brine (100 mL), dried (Na2SO4), filtered and concentrated to give yellow liquid. This was purified by flash column chromatography on silica gel column using (10-40% EtOAc/Hex as eluant) to afford the desired (S)-methyl 2-(tert-butoxy)-2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (735 mg, 1.663 mmol, 72.3% yield) as white solid. 150 mg of starting material was also recovered. 1H NMR (500 MHz, CDCl3) δ: 7.76-7.70 (m, 2H), 7.18 (d, J=7.9 Hz, 1H), 6.91 (s, 1H), 5.68 (s, 1H), 3.76 (s, 3H), 2.89-2.84 (m, 4H), 2.68 (s, 3H), 1.89-1.83 (m, 4H), 1.30 (s, 9H). LCMS (M+H)=444.3.

Workup

  1. customcarefully quenched with sat. NaHCO3 (50 mL), organic layer
  2. customseparated
  3. washwashed with brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give yellow liquid
  8. customThis was purified by flash column chromatography on silica gel column

Sources & evidence

ORD record
ord-91de0fe2a18846b4b3ab1a212669979c
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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