Lithium iodide → Tert-butyl 4-(1-aminocyclopropyl)benzoate

HRID 1921669Notes

Reaction equation

HRID 1921669 reaction equation
[CH3:1][CH:2](C)[O-].[Li+].[I-].[Li+].[C:8]([C:10]1[CH:22]=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:12][CH:11]=1)#[N:9].C([Zn]CC)C>C1COCC1.CCCCCC.CC(C)[O-].C[Ti+3].CC(C)[O-].CC(C)[O-].O>[NH2:9][C:8]1([C:10]2[CH:22]=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])=[CH:12][CH:11]=2)[CH2:2][CH2:1]1

Participants

9

Reactant 4

HCID 66321Lithium iodideHCID 271408Tert-butyl 4-cyanobenzoateHCID 23673350Lithium propan-2-olateHCID 178418750HCID 178418750, compound

Product 1

HCID 59305811Tert-butyl 4-(1-aminocyclopropyl)benzoate

Reagents, catalysts & solvents 4

HCID 178459133HCID 178459133, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

50 mL of a 2M lithium isopropoxide solution in THF was placed under an argon atmosphere and 13.4 g of anhydrous lithium iodide was added thereto. After 15 minutes, 45 mL of a 1M methyltitanium isopropoxide solution in THF was added. Then the mixture was combined with 8.1 g of tert-butyl 4-cyanobenzoate and stirred for 10 minutes. Then within 60 minutes, 47.3 mL of a 15% diethylzinc solution in hexane was added thereto and the mixture was stirred for 12 hours at RT. After hydrolysis with 20 mL of water, it was stirred for a further 30 minutes, filtered off, and washed 3× with 100 mL of ether. After extraction of the organic phase with water, the mixture was evaporated down with silica gel and the substance was chromatographed with dichloromethane/methanol (98:2) at 20 mL/min on silica gel 70. Residue: 3 g oil.

Workup

  1. waitThen within 60 minutes
  2. stirringthe mixture was stirred for 12 hours at RT
  3. stirringwas stirred for a further 30 minutes
  4. filtrationfiltered off
  5. washwashed 3× with 100 mL of ether
  6. extractionAfter extraction of the organic phase with water
  7. customthe mixture was evaporated down with silica gel
  8. customthe substance was chromatographed with dichloromethane/methanol (98:2) at 20 mL/min on silica gel 70

Sources & evidence

ORD record
ord-a90a8568033f448e96b5a8f58a54447f
Source dataset
uspto-grants-2012_05
Patent number
US08173699B2

Reaction notes

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