(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole toluene → (S)-methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 1400692Notes

Reaction equation

HRID 1400692 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:17](=[O:22])[C:18]([O:20][CH3:21])=[O:19])=[C:15]([I:16])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.C1(C)C=CC=CC=1>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])([O-])=O.[Na+].[Na+]>[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]([I:16])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 86670277(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole tolueneHCID 86710744Methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate

Product 1

HCID 86710745(S)-methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetateYield 58.6%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
-35 °C

Procedure

To a stirred yellow solution of methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (1.7 g, 3.40 mmol) in anhydrous toluene (100 mL) was added 1.1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (1.236 mL, 1.360 mmol). The mixture was cooled to −35° C. and a solution of catechoborane/toluene (1.166 mL, 4.76 mmol) was added over 5 min. After 30 min, the reaction mixture was slowly warmed to −15° C. and stirred for additional 2 h. and diluted with EtOAc (600 mL) and sat. Na2CO3 (100 mL). The mixture was stirred vigorously for 30 min, and the organic phase washed with sat Na2CO3 (2×100 mL), dried (Na2SO4), filtered, concentrated and the residue was purified by silica gel chromatography (5-100% EtOAc/hexane) to afford desired (S)-methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (1 g, 1.992 mmol, 58.6% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ: 8.21 (t, J=1.7 Hz, 1H), 7.96 (dt, J=7.8, 1.2 Hz, 1H), 7.59-7.55 (m, 1H), 7.37 (t, J=7.8 Hz, 1H), 7.09 (s, 1H), 5.78 (s, 1H), 3.87 (s, 3H), 3.54 (br. s., 1H), 2.61 (s, 3H). LCMS (M+H)=504.05.

Workup

  1. temperaturethe reaction mixture was slowly warmed to −15° C.
  2. stirringThe mixture was stirred vigorously for 30 min
  3. washthe organic phase washed
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified by silica gel chromatography (5-100% EtOAc/hexane)

Sources & evidence

ORD record
ord-562b5660549d42908cc6299a73ea6da6
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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