Sodium Carbonate → HCID 117626446, compound

HRID 921069Notes

Reaction equation

HRID 921069 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[C:5]([C:7]1[C:8]([CH3:22])=[N:9][C:10]2[N:11]([N:14]=[C:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:16]=2)[C:12]=1[Cl:13])=[O:6])[CH3:2].CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:13][C:12]1[N:11]2[N:14]=[C:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:16]=[C:10]2[N:9]=[C:8]([CH3:22])[C:7]=1[C@H:5]([OH:6])[C:4]([O:3][CH2:1][CH3:2])=[O:23]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 86670277(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole tolueneHCID 117604155HCID 117604155, compound

Product 1

HCID 117626446HCID 117626446, compoundYield 75.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-35 °C

Procedure

To a stirred yellow solution of ethyl 6-(2-ethoxy-2-oxoacetyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (264 mg, 0.777 mmol) in anhydrous toluene (5 mL) was added 1.0M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.311 mL, 0.311 mmol). The mixture was cooled to −35° C. and a solution of 50% catechoborane/toluene (0.272 mL, 1.088 mmol) was added over the course of 10 min. After 30 min, the reaction mixture was slowly warmed to −15° C. and stirred for additional 2 h, then diluted with EtOAc (30 mL) and sat.aq. Na2CO3 (5 mL). The mixture was stirred vigorously for 30 min, and the organic phase was washed with sat. aq. Na2CO3 (2×5 mL), dried (Na2SO4), filtered, concentrated. The residue was purified by silica gel chromatography (5-100% EtOAc/hexane) to afford the desired (S)-ethyl 7-chloro-6-(2-ethoxy-1-hydroxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (200 mg, 0.585 mmol, 75% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 7.21 (s, 1H), 5.77 (d, J=2.7 Hz, 1H), 4.53 (d, J=7.1 Hz, 2H), 4.33 (dd, J=7.1, 5.5 Hz, 2H), 3.61 (br. s., 1H), 2.68 (s, 3H), 1.50-1.46 (t, J=7.09 Hz, 3H), 1.28 (t, J=7.09 Hz, 3H). LCMS (M+1)=342.13.

Workup

  1. temperaturethe reaction mixture was slowly warmed to −15° C.
  2. stirringThe mixture was stirred vigorously for 30 min
  3. washthe organic phase was washed with sat. aq. Na2CO3 (2×5 mL)
  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-48915c3ae90943a0a8aadec9327a25e3
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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