Trimethyl borate → HCID 90412649, compound

HRID 1746638Notes

Reaction equation

HRID 1746638 reaction equation
[C:1]([Si:5]([O:18][C@@H:19]1[C@H:26]2[C@H:22]([O:23][C:24]([CH3:28])([CH3:27])[O:25]2)[C:21]([CH2:29][O:30][C:31]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[C:20]1I)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2].C[O:52][B:53](OC)[O:54]C>C1COCC1>[Si:5]([O:18][C@@H:19]1[C@@H:26]2[O:25][C:24]([CH3:27])([CH3:28])[O:23][C@@H:22]2[C:21]([CH2:29][O:30][C:31]([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)=[C:20]1[B:53]([OH:54])[OH:52])([C:1]([CH3:4])([CH3:2])[CH3:3])([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

4

Reactant 2

HCID 8470Trimethyl borateHCID 90412667HCID 90412667, compound

Product 1

HCID 90412649HCID 90412649, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 100 mL round-bottom 3-neck flask equipped with nitrogen inlet/outlet, stir bar, and thermocouple with temperature controller was charged 3.0877 g of compound 8 (3 mmol, 1.0 eq) and 30 mL tetrahydrofuran (10 V). Reaction was cooled to 0° C. To this solution was added 6.98 mL (9 mmol, 2.4 eq) of isopropylmagnesium chloride lithium chloride complex, 1.3 M in THF slowly over 15 minutes. The reaction was stirred at 0° C. for 1 hour. An HPLC assay indicated the formation of intermediate. 1.05 mL of trimethylborate (9 mmol, 2.5 eq) was added to the reaction. An HPLC assay after 1 hour at 0° C. indicated that the reaction was completed. Quenched reaction with saturated aqueous ammonium chloride solution (3V). The ice bath was removed and the reaction was warmed to room temperature. The reaction was charged with DI water (3V) and ethyl acetate (6V). The layers were separated and the aqueous layer was back-extracted with ethyl acetate (6V). The organic phases were combined and washed with brine (3V) and dried over MgSO4. The resulting mixture was filtered. The filtrate was concentrated to dryness with a rotary evaporator. Obtained 2.87 grams (100% crude yield), 96 A % purity of [(3aR,6S,6aR)-6-[tert-butyl(diphenyl)silyl]oxy-2,2-dimethyl-4-(trityloxymethyl)-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-5-yl]boronic acid (compound 9c-1).

Workup

  1. customTo a 100 mL round-bottom 3-neck flask equipped with nitrogen inlet/outlet
  2. customReaction
  3. stirringThe reaction was stirred at 0° C. for 1 hour
  4. customQuenched
  5. customreaction with saturated aqueous ammonium chloride solution (3V)
  6. customThe ice bath was removed
  7. temperaturethe reaction was warmed to room temperature
  8. additionThe reaction was charged with DI water (3V) and ethyl acetate (6V)
  9. customThe layers were separated
  10. extractionthe aqueous layer was back-extracted with ethyl acetate (6V)
  11. washwashed with brine (3V)
  12. dry with materialdried over MgSO4
  13. filtrationThe resulting mixture was filtered
  14. concentrationThe filtrate was concentrated to dryness with a rotary evaporator

Sources & evidence

ORD record
ord-2afbd9a29e8344cd82f8e7fdbd90bbfe
Source dataset
uspto-grants-2015_10
Patent number
US09150520B2

Reaction notes

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