2-Methyl-2-butene → (1S,2R)-4'-(4-Chlorophenyl)-2',3',9'-trimethylspiro[cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]-2-carboxylic acid

HRID 1772337Notes

Reaction equation

HRID 1772337 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[C:15]([CH3:19])=[C:16]([CH3:18])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[C@@:10]3([CH2:25][C@H:24]3[CH:26]=[O:27])[N:9]=2)=[CH:4][CH:3]=1.CC(=CC)C.Cl([O-])=[O:34].[Na+]>CC(O)(C)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:14]3[C:15]([CH3:19])=[C:16]([CH3:18])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[C@@:10]3([CH2:25][C@H:24]3[C:26]([OH:34])=[O:27])[N:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 86706921(1S,2R)-4'-(4-Chlorophenyl)-2',3',9'-trimethylspiro[cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]-2-carbaldehyde

Product 1

HCID 57404934(1S,2R)-4'-(4-Chlorophenyl)-2',3',9'-trimethylspiro[cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

To a solution of crude (1S,2R)-4′-(4-chlorophenyl)-2′,3′,9′-trimethylspiro[cyclopropane-1,6′-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]-2-carbaldehyde (298 mg, 0.752 mmol) in t-BuOH (5 mL) was added 2-methylbut-2-ene (1055 mg, 15.04 mmol) and a pH 7 buffer solution (5 mL). Then sodium chlorite was added at rt, and the biphasic reaction was vigorously stirred for 3.5 h. When the starting material was entirely consumed, sat. aq. NH4Cl was added, and the product was extracted with DCM/MeOH (19:1) (repeated 3 times). The organic layers were combined, dried over Na2SO4, filtered and concentrated to dryness. The residue was used in the next step without purification. LRMS (M+H)+: 413 m/z.

Workup

  1. customthe biphasic reaction
  2. customWhen the starting material was entirely consumed
  3. additionsat. aq. NH4Cl was added
  4. extractionthe product was extracted with DCM/MeOH (19:1) (repeated 3 times)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe residue was used in the next step without purification

Sources & evidence

ORD record
ord-6d662412a1e34ea3a393359a7ea71e3f
Source dataset
uspto-grants-2016_02
Patent number
US09249161B2

Reaction notes

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