Methanol → {4-[4-Chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]cyclohex-3-en-1-yl}methanol

HRID 1626983Notes

Reaction equation

HRID 1626983 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]1[CH2:20][CH2:19][CH:18]([C:21](OC)=[O:22])[CH2:17][CH:16]=1.CO.[BH4-].[Li+].C(=O)(O)[O-].[Na+]>ClCCl.O>[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:13][CH2:14]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]1[CH2:20][CH2:19][CH:18]([CH2:21][OH:22])[CH2:17][CH:16]=1

Participants

7

Reactant 4

HCID 887Methanol2×HCID 516892Sodium BicarbonateHCID 4148881Lithium borohydride2×HCID 70978021HCID 70978021, compound

Product 1

HCID 70977902{4-[4-Chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]cyclohex-3-en-1-yl}methanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl 4-[4-chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]cyclohex-3-ene-1-carboxylate (Example 1, 0.22 g, 0.64 mmol) was dissolved in dichloromethane (10 mL), treated with methanol (0.031 mL, 0.77 mmol, 1.2 equiv) and then lithium borohydride (17 mg, 0.77 mmol, 1.2 equiv). The mixture was stirred at ambient temperature for 30 minutes. To the mixture, eight additional portions of lithium borohydride (17 mg, 0.77 mmol, 1.2 equiv) and eight additional portions of methanol (0.031 mL, 0.77 mmol, 1.2 equiv) were added over 4 hours. The mixture was treated with sodium bicarbonate (20 mL, aqueous saturated), stirred for 18 hours and poured into water (100 mL), which was extracted with ethly acetate (2×100 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 7.87 (1H, d, J=8.6 Hz), 7.41 (1H, d, J=8.6 Hz), 5.75-5.72 (1H, m), 4.61 (2H, d, J=7.3 Hz), 3.44-3.37 (1H, m), 3.36-3.32 (1H, m), 2.43-2.33 (1H, m), 2.33-2.23 (2H, m), 1.94-1.85 (2H, m), 1.82-1.74 (1H, m), 1.47-1.34 (2H, m), 0.58-0.53 (2H, m), 0.49-0.45 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 318.1368 [(M+H)+; calculated for C17H21ClN3O: 318.1368].

Workup

  1. stirringstirred for 18 hours
  2. extractionwas extracted with ethly acetate (2×100 mL)
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-dd4102b098dd4e329a972b8b9222478c
Source dataset
uspto-grants-2014_07
Patent number
US08785482B2

Reaction notes

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