Triphenylphosphine → 3-(7-bromo-5-fluoro-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester

HRID 2089483Notes

Reaction equation

HRID 2089483 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][CH:9]2O)=[C:4]([F:13])[CH:3]=1.[NH:14]1[CH:18]=[C:17]([C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20])[N:16]=[CH:15]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC)=O)=NC([O-])=O>C1COCC1>[CH:22]([O:21][C:19]([C:17]1[N:16]([CH:9]2[C:10]3[C:5](=[C:4]([F:13])[CH:3]=[C:2]([Br:1])[CH:11]=3)[CH2:6][CH2:7][CH2:8]2)[CH:15]=[N:14][CH:18]=1)=[O:20])([CH3:24])[CH3:23]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 675473967-bromo-5-fluoro-3,4-dihydro-2H-naphthalen-1-olHCID 86639266Methyl azodicarboxylateHCID 178459416HCID 178459416, compound

Product 1

HCID 591994533-(7-bromo-5-fluoro-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-bromo-5-fluoro-3,4-dihydro-2H-naphthalen-1-ol (0.280 g, 1.10 mmol) and isopropyl 4-imidazolecarboxylate (0.121 g, 0.77 mmol), which can be prepared as described in Example 1, in THF (6 mL) at 0° C. is added triphenylphosphine (0.291 g, 1.10 mmol) and methyl azodicarboxylate (40% in toluene, 0.41 mL, 1.10 mmol). After 1 hour, the cooling bath is removed and after another hour, the mixture is diluted with ethyl acetate and washed with half-saturated brine, dried over magnesium sulfate, filtered, t and concentrated. The resulting residue is purified by semi-preparative reverse phase HPLC (5 to 100% acetonitrile/water w/0.1% TFA) to furnish affords a pale yellow oil. After free-basing, 3-(7-bromo-5-fluoro-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester is obtained; MS: (ESI) m/z 381.1, 383.0 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 1.37 (d, J=6.3 Hz, 3 H), 1.39 (d, J=6.3 Hz, 3 H), 1.71-1.81 (m, 1 H), 1.83-1.92 (m, 1 H), 2.07-2.24 (m, 2 H), 2.72 (dt, J=17.7, 6.8 Hz, 1 H), 2.87 (dd, J=17.7, 5.8 Hz, 1 H), 5.22 (sept, J=6.3 Hz, 1 H), 6.29 (t, J=5.2 Hz, 1 H), 6.94 (br. s, 1 H), 7.18 (dd, J=8.8, 1.8 Hz, 1 H), 7.22 (s, 1 H), 7.79 (s, 1 H).

Workup

  1. customthe cooling bath is removed and after another hour
  2. additionthe mixture is diluted with ethyl acetate
  3. washwashed with half-saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationt and concentrated
  7. customThe resulting residue is purified by semi-preparative reverse phase HPLC (5 to 100% acetonitrile/water w/0.1% TFA)
  8. customto furnish
  9. customaffords a pale yellow oil

Sources & evidence

ORD record
ord-c02a3e89fc60499aa07a556511b6132b
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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