Trimethyl borate → HCID 178454343, compound

HRID 389485Notes

Reaction equation

HRID 389485 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[N:17]=[CH:18][C:19]([C:25]2[CH:26]=[N:27][N:28]([C@H:30]3[CH2:35][CH2:34][C@H:33]([O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[CH2:32][CH2:31]3)[CH:29]=2)=[C:20]2[CH:24]=[CH:23][O:22][C:21]=12)[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].[B:52](OC)([O:55]C)[O:53]C>C1COCC1>[C:1]([O:5][C:6]([N:8]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:16]1[N:17]=[CH:18][C:19]([C:25]2[CH:26]=[N:27][N:28]([C@H:30]3[CH2:35][CH2:34][C@H:33]([O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[CH2:32][CH2:31]3)[CH:29]=2)=[C:20]2[CH:24]=[C:23]([B:52]([OH:55])[OH:53])[O:22][C:21]=12)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 8470Trimethyl borateHCID 2724682Lithium diisopropylamideHCID 178454344HCID 178454344, compound

Product 1

HCID 178454343HCID 178454343, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (−78° C.) solution of di-tert-butyl{4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]furo[2,3-c]pyridin-7-yl}imidodicarbonate (1 g, 2 mmol) in anhydrous THF (10 mL) was added lithium diisopropylamide (2 M in THF, 1.47 mL, 2.94 mmol), and the mixture stirred for 30 min. Boric acid, trimethyl ester (0.371 mL, 3.26 mmol) was added, and the mixture stirred for 10 min before warming to 0° C. The mixture was quenched with water (0.2 mL) and warmed to RT. The THF was removed by rotary evaporation, and the residue was partitioned between ethyl acetate and water. Following separation of the layers, the organic layer was dried over sodium sulfate and evaporated. To the resulting foam was added heptane, and the solution was stirred until the particles were reduced to a powdery solid. The mixture was filtered and washed with heptane (10×). The solid was dried under vacuum to afford 0.6 g (60%) of the title compound as a beige solid. 1H NMR (400 MHz, CD3OD): δ 8.23 (s, 1 H), 8.22 (s, 1 H), 8.01 (s, 1 H), 7.07 (s, 1 H), 4.39-4.18 (m, 1 H), 3.93-3.70 (m, 1 H), 2.26-2.13 (m, 2 H), 2.11-1.92 (m, 4 H), 1.60-1.53 (m, 2 H), 1.33 (s, 18 H), 0.93 (s, 9 H), 0.12 (s, 6 H).

Workup

  1. stirringthe mixture stirred for 10 min
  2. customThe mixture was quenched with water (0.2 mL)
  3. temperaturewarmed to RT
  4. customThe THF was removed by rotary evaporation
  5. customthe residue was partitioned between ethyl acetate and water
  6. customseparation of the layers
  7. dry with materialthe organic layer was dried over sodium sulfate
  8. customevaporated
  9. additionTo the resulting foam was added heptane
  10. stirringthe solution was stirred until the particles
  11. filtrationThe mixture was filtered
  12. washwashed with heptane (10×)
  13. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-acb64ec580fc4c3cac4905aaf7484c9f
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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