Triethylamine → tert-Butyl 3-methyl-1H-indazole-1-carboxylate

HRID 343112Notes

Reaction equation

HRID 343112 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][N:3]=1.CCN(CC)CC.[O:18](C(OC(C)(C)C)=O)[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=O>CC#N.CN(C1C=CN=CC=1)C>[C:22]([O:21][C:19]([N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2]([CH3:1])=[N:3]1)=[O:18])([CH3:25])([CH3:24])[CH3:23]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 178434273HCID 178434273, compound

Product 1

HCID 10775939tert-Butyl 3-methyl-1H-indazole-1-carboxylateYield 100%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirring solution of 30.3 g (0.23 mol) of 3-methylindazole, prepared as in Part A, in 300 mL of CH3CN is added 35.0 mL (0.25 mol, 1.1 equiv) of Et3N and 5.77 g (47.2 mmol, 0.2 equiv) of DMAP, and the mixture is cooled to 0° C. 60.5 g (0.28 mol, 1.2 equiv) of (BOC)2O in 200 mL CH3CN is added dropwise with stirring at 0° C. and the resultant reaction mixture stirred 3 h at RT. The solvent is removed in vacuo and the crude material partitioned between Et2O (300 mL) and H2O (100 mL). The pH is adjusted to 2.0 with 1N HCl, the organic phase separated, dried (MgSO4), filtered and concentrated in vacuo to an orange oil which is purified by filtration through a pad of silica gel using Hexane/EtOAc 4/1 as eluent. The filtrate is concentrated in vacuo to give 53.4 g of 1-tert-butoxycarbonyl-3-methylindazole as a white solid: 1H NMR (CDCl3, 300 MHz) δ8.15 (d, 1H, J=7.8), 7.67 (d, 1H, J=7.8), 7.56 (dd, 1H, J=7.3, 7.3), 7.35 (dd, 1H, J=7.3, 7.3), 2.62 (s, 3H), 1.77 (s, 9H); TLC Rf =0.66 (EtOAc/Hexane 1/2).

Workup

  1. customthe resultant reaction mixture
  2. stirringstirred 3 h at RT
  3. customThe solvent is removed in vacuo
  4. customthe crude material partitioned between Et2O (300 mL) and H2O (100 mL)
  5. customthe organic phase separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to an orange oil which
  9. filtrationis purified by filtration through a pad of silica gel
  10. concentrationThe filtrate is concentrated in vacuo

Sources & evidence

ORD record
ord-e921633af65242b48ce2c99bab8c1a4e
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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