Iodine → HCID 67981148, compound

HRID 1427435Notes

Reaction equation

HRID 1427435 reaction equation
[Mg].II.Br[CH:5]1[CH2:8][CH2:7][CH2:6]1.C[C:10]1[CH:15]=[C:14]([C:16]#[N:17])[CH:13]=[CH:12][C:11]=1[C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1.[BH4-].[Na+]>C(OCC)C.O1CCCC1.CO>[CH:5]1([CH:16]([C:14]2[CH:15]=[CH:10][C:11]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:25])([F:26])[F:27])=[CH:20][CH:19]=3)=[CH:12][CH:13]=2)[NH2:17])[CH2:8][CH2:7][CH2:6]1

Participants

9

Reactant 5

HCID 807IodineHCID 78110BromocyclobutaneHCID 4311764Sodium borohydrideHCID 5462224MagnesiumHCID 67981173HCID 67981173, compound

Product 1

HCID 67981148HCID 67981148, compoundYield 27.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

Magnesium (1.86 g, 77.4 mmol) was suspended in diethyl ether (70 mL) and to the suspension was added iodine (17.8 mg, 0.07 mmol). Bromo-cyclobutane (10 g, 70 mmol) was added slowly and the mixture was refluxed for 3 h. To a solution of 4′-(trifluoromethyl)biphenyl-4-carbonitrile (300 mg, 1.21 mmol) (prepared as in Example 1.25 Step A, using 4-bromobenzonitrile) in tetrahydrofuran (3 mL) was added this prepared Grignard (334 mg, 6.06 mL in diethyl ether, 6.06 mmol) at 0° C. under nitrogen. The resulting mixture was heated in a microwave at 100° C. for 1 hr. After that time, methanol (5 mL) and sodium borohydride (91.8 mg, 2.43 mmol) were carefully added at 0° C. After stirring for 5 minutes, the reaction mixture was quenched with saturated ammonium chloride (20 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were concentrated. Purification by column chromatography (0-6% methanol/dichloromethane) gave cyclobutyl(4′-(trifluoromethyl)biphenyl-4-yl)methanamine (0.100 g, 27%) as a yellow solid.

Workup

  1. temperaturethe mixture was refluxed for 3 h
  2. customthe reaction mixture was quenched with saturated ammonium chloride (20 mL)
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. concentrationThe combined organic layers were concentrated
  5. customPurification by column chromatography (0-6% methanol/dichloromethane)

Sources & evidence

ORD record
ord-275e7eca2ac749f7b2f2ed7971fb25fb
Source dataset
uspto-grants-2015_01
Patent number
US08933104B2

Reaction notes

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