Benzyl Alcohol → HCID 71209169, compound

HRID 1912630Notes

Reaction equation

HRID 1912630 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH3:14])[C:6]=1C(O)=O)=[O:4].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:25])C=CC=CC=1.CC[N:37]([CH2:40]C)CC.[CH2:42]([OH:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C)C=O>[CH2:42]([O:49][C:40]([NH:37][C:6]1[N:7]([CH3:14])[C:8]2[C:13]([C:5]=1[C:3]([O:2][CH3:1])=[O:4])=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:25])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 71209434HCID 71209434, compound

Product 1

HCID 71209169HCID 71209169, compoundYield 79.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

An ice cold solution of 3-(methoxycarbonyl)-1-methyl-1H-indole-2-carboxylic acid (1.0 g, 4.29 mmol) in N,N-dimethylformamide (DMF) (40.5 ml) was treated with diphenylphosphoryl azide (DPPA) (1.016 ml, 4.72 mmol) and Et3N (0.654 ml, 4.72 mmol) and then warmed to ambient temperature. After 2 h, the reaction mixture was treated with benzyl alcohol (0.713 ml, 6.86 mmol) and warmed to 80° C. After 3 h, the reaction mixture was cooled to ambient temperature and partitioned between 1 M HCl and EtOAc. The organic layer was washed with sat. aq. NaHCO3, brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by ISCO (0-50% EtOAc-hexanes) to afford methyl 2-(((benzyloxy)carbonyl)amino)-1-methyl-1H-indole-3-carboxylate (1.15 g, 3.40 mmol, 79% yield) and a yellow oil. The residue was dissolved in MeOH (20 mL), treated with Pd/C (0.362 g, 0.34 mmol) and then purged/backfilled with N2 3× and pressurized to 50 psi of H2. After 18 h, the reaction mixture was filtered and concentrated in vacuo to afford methyl 2-amino-1-methyl-1H-indole-3-carboxylate (426 mg, 2.086 mmol, 48.6% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ=6.98 (m, 4 H), 3.77 (s, 3 H), 3.34 (s, 3 H); LCMS (m/z) ES+=205 (M+1).

Workup

  1. temperaturewarmed to 80° C
  2. waitAfter 3 h
  3. temperaturethe reaction mixture was cooled to ambient temperature
  4. custompartitioned between 1 M HCl and EtOAc
  5. washThe organic layer was washed with sat. aq. NaHCO3, brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by ISCO (0-50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-717dfc20163546a99fff36fda130e4db
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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