Benzyl Alcohol → benzyl (2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)carbamate

HRID 2068880Notes

Reaction equation

HRID 2068880 reaction equation
[CH3:1][C:2]1([CH3:39])[CH2:10][C:9]2[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:7]=[C:6]([C:19]3[N:20]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:21]4[C:26]([CH:27]=3)=[CH:25][CH:24]=[C:23](C(O)=O)[CH:22]=4)[C:5]=2[CH2:4][CH2:3]1.C([N:42]([CH2:45]C)CC)C.[CH2:47]([OH:54])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:62])C=CC=CC=1>C1(C)C=CC=CC=1.O>[CH3:1][C:2]1([CH3:39])[CH2:10][C:9]2[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:17])([CH3:16])[CH3:18])[N:7]=[C:6]([C:19]3[N:20]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:37])([CH3:38])[CH3:36])[C:21]4[C:26]([CH:27]=3)=[CH:25][CH:24]=[C:23]([NH:42][C:45](=[O:62])[O:54][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[CH:22]=4)[C:5]=2[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 585502432-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid

Product 1

HCID 86660209benzyl (2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indol-6-yl)carbamateYield 92.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Under an argon atmosphere, to a solution of 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid (26 g, 45 mmol), triethylamine (8.2 ml, 59 mmol) and benzyl alcohol (18 ml, 180 mmol) in toluene (260 ml) was added dropwise diphenylphosphoryl azide (12 ml, 54 mmol) at 115° C. over 2 hr. After cooling, water was added to the reaction mixture, and the organic layer was separated. Then, the organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography, and slurry-washed in hexane (210 ml) with heating at 60° C. The resulting crystals were collected by filtration, washed with hexane, and dried under reduced pressure to give the title compound (28 g, yield 91%).

Workup

  1. temperatureAfter cooling
  2. customthe organic layer was separated
  3. washThen, the organic layer was washed successively with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. customMagnesium sulfate was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washslurry-washed in hexane (210 ml)
  9. filtrationThe resulting crystals were collected by filtration
  10. washwashed with hexane
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-d1aed978d322487283c5d91371cebb67
Source dataset
uspto-grants-2012_10
Patent number
US08299070B2

Reaction notes

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