Trimethyl borate → tert-butyl-[2-(1H-indol-5-yl)propan-2-yloxy]silane;[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid

HRID 431168Notes

Reaction equation

HRID 431168 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]([CH3:25])([CH3:24])[O:18][SiH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.C[O:34][B:35](OC)[O:36]C>O1CCCC1>[C:20]([SiH2:19][O:18][C:17]([CH3:25])([CH3:24])[C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[NH:8][CH:9]=[CH:10]2)([CH3:23])([CH3:21])[CH3:22].[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[B:35]([OH:36])[OH:34])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8470Trimethyl borateHCID 5062348DiisopropylamideHCID 131722897Tert-butyl 5-(2-tert-butylsilyloxypropan-2-yl)indole-1-carboxylate

Product 1

HCID 157380136tert-butyl-[2-(1H-indol-5-yl)propan-2-yloxy]silane;[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acidYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 5-(tert-Butyl-dimethyl-silanyloxymethyl)-indole-1-carboxylic acid tert-butyl ester (3-3, 38.6 g, 106.7 mmol) in tetrahydrofuran (400 mL) was slowly added at −78 deg C. a solution of lithiun diisopropylamide in tetrahydrofuran (2M, 80.1 mL, 160.1 mmol, 1.5 equiv). The reaction mixture was stirred at the same temperature for 1 h, treated with trimethylborate, warmed up to ambient temperature, and partitioned between ethyl acetate and 0.5N-HCl. The organic layer was washed with brine, separated, dried (MgSO4) and concentrated in vacuo to give the crude solid. Trituration of the crude product with hexanes followed by filtration and air-drying afforded the desired boronic acid (3-4, 41.3 g, 95%) as a white powder; 1H NMR (400 MHz, CDCl3) δ 7.96 (d, 1H, J=6.8 Hz), 7.54 (s, 1H), 7.47 (s, 1H), 7.32 (d, 1H, J=6.8 Hz), 7.10 (s, 1H), 4.82 (s, 2H), 1.74 (s, 9H), 0.95 (s, 9H), 0.11 (s, 6H).

Workup

  1. custompartitioned between ethyl acetate and 0.5N-HCl
  2. washThe organic layer was washed with brine
  3. customseparated
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto give the crude solid
  7. filtrationTrituration of the crude product with hexanes followed by filtration
  8. customair-drying

Sources & evidence

ORD record
ord-ee3ae2910ff042faa2d1131dafcec169
Source dataset
uspto-grants-2003_12
Patent number
US06656942B2

Reaction notes

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