tert-Butyl acetate → (S)-Methyl 2-(2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 1400724Notes

Reaction equation

HRID 1400724 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:24]=[C:11]3[N:12]=[C:13]([CH3:23])[C:14]([C@H:17]([OH:22])[C:18]([O:20][CH3:21])=[O:19])=[C:15]([Cl:16])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:25](OC(=O)C)([CH3:28])([CH3:27])[CH3:26].Cl(O)(=O)(=O)=O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:24]=[C:11]3[N:12]=[C:13]([CH3:23])[C:14]([C@H:17]([O:22][C:25]([CH3:28])([CH3:27])[CH3:26])[C:18]([O:20][CH3:21])=[O:19])=[C:15]([Cl:16])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 86710773(S)-methyl 2-(2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Product 1

HCID 86710775(S)-Methyl 2-(2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateYield 64.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-methyl 2-(2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (7.81 g, 19.02 mmol), t-butylacetate (160 mL) in DCM (330 mL) was added perchloric acid (3.43 mL, 57.1 mmol) and the mixture was stirred at rt for 3 h. It was then quenched with sat.aq.NaHCO3 (adjusted to pH=7-8 by the addition of solid NaHCO3). This mixture was diluted with EtOAc and the organic phase was washed with water. The organic phase was dried (MgSO4), filtered, and concentrated in vacuo to obtain ˜7 g of crude product as an oil. Filtration through 70 g of silica gel eluting with CH2Cl2 gave (S)-methyl 2-(2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (5.71 g, 12.23 mmol, 64.3% yield). 1H NMR (400 MHz, CDCl3) δ 8.20 (t, J=1.6 Hz, 1H), 7.95 (dt, J=7.8, 1.1 Hz, 1H), 7.63-7.53 (m, 1H), 7.37 (t, J=7.9 Hz, 1H), 6.94 (s, 1H), 5.69 (s, 1H), 3.76 (s, 3H), 2.70 (s, 3H), 1.30 (s, 9H). LCMS (M+H)=466 and 468.

Workup

  1. customIt was then quenched with sat.aq
  2. additionNaHCO3 (adjusted to pH=7-8 by the addition of solid NaHCO3)
  3. additionThis mixture was diluted with EtOAc
  4. washthe organic phase was washed with water
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto obtain ˜7 g of crude product as an oil
  9. filtrationFiltration through 70 g of silica gel eluting with CH2Cl2

Sources & evidence

ORD record
ord-0ff2691f9b4f43ac8f28a73538f67c19
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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