Perchloric Acid → (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 1400756Notes

Reaction equation

HRID 1400756 reaction equation
[CH2:1]([O:4][C:5]1([CH3:35])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([Br:26])[CH:21]=4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:27])[C:12]=2[C@H:28]([OH:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].Cl(O)(=O)(=O)=O>C(Cl)Cl.C(OC(C)(C)C)(=O)C>[CH2:1]([O:4][C:5]1([CH3:35])[CH2:6][CH2:7][N:8]([C:11]2[N:16]3[N:17]=[C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([Br:26])[CH:21]=4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:27])[C:12]=2[C@H:28]([O:34][C:5]([CH3:35])([CH3:10])[CH3:6])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:9][CH2:10]1)[CH:2]=[CH2:3]

Participants

5

Reactant 2

HCID 24247Perchloric AcidHCID 86710814(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Product 1

HCID 86710813(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 106.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 10908tert-Butyl acetateSolvent

Procedure

To a stirred solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (8.5 g, 15.64 mmol) in DCM (250 mL) and t-butyl acetate (175 mL) was added perchloric acid (4.03 mL, 46.9 mmol) at rt. After 3 h, the reaction mixture was diluted with DCM (100 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 chromatograpgy on silica gel column using (10-50% EtOAc/Hex as eluant) to afford the desired (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (5 g, 8.34 mmol, 53.3% yield) as light yellow solid. 3 g of starting material was also recovered. 1H NMR (500 MHz, CDCl3) δ 8.23-8.11 (m, 1H), 7.94 (d, J=7.7 Hz, 1H), 7.56-7.51 (m, 1H), 7.33 (t, J=7.9 Hz, 1H), 6.81 (s, 1H), 6.10 (br. s., 1H), 6.00 (br. s., 1H), 5.49 (d, J=16.6 Hz, 1H), 5.28 (d, J=10.2 Hz, 1H), 4.30-4.14 (m, 2H), 4.10-4.00 (m, 2H), 2.65 (s, 3H), 2.09-1.85 (m, 3H), 1.74 (br. s., 1H), 1.38 (s, 3H), 1.28-1.16 (m, 12H). 4 missing piperidine hydrogens. LCMS (M+H)=601.5.

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 chromatograpgy on silica gel column

Sources & evidence

ORD record
ord-66fa35b3b0614d05a230551b5af39dbe
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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