Triphenylphosphine → 1-[(4-chloro-6-methoxyquinolin-7-yloxy)methyl]-N-benzyloxycarbonyl-1-aminocyclopropane

HRID 239015Notes

Reaction equation

HRID 239015 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:14])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[CH2:15]([O:22][C:23]([NH:25][C:26]1([CH2:29]O)[CH2:28][CH2:27]1)=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C(Cl)Cl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:29][C:26]3([NH:25][C:23]([O:22][CH2:15][C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)=[O:24])[CH2:27][CH2:28]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 22178711Benzyl (1-(hydroxymethyl)cyclopropyl)carbamateHCID 1355837314-Chloro-6-methoxyquinolin-7-ol

Product 1

HCID 469123041-[(4-chloro-6-methoxyquinolin-7-yloxy)methyl]-N-benzyloxycarbonyl-1-aminocyclopropaneYield 46.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

20 ml of DCM were added with 4-chloro-7-hydroxy-6-methoxyquinoline (300 mg, 1.43 mmol; from China Gateway), 1-benzyloxycarbonylamino-1-hydroxymethylcyclopropane (412 mg, 1.87 mmol, 1.3 eq; from China Gateway) and triphenylphosphine (490 mg, 1.87 mmol, 1.3 eq). The resulting solution was dropwise added with a solution of DEAD (378 mg, 1.87 mmol, 1.3 eq) in 3 ml of DCM, keeping the temperature at 0° C. for 2 hours. The mixture was then left at 10° C. for 20 hours, then filtered to recover the unreacted 4-chloro-7-hydroxy-6-methoxyquinoline. The filtrate was evaporated under vacuum and the resulting residue was added with 20 ml of 95% EtOH and left under stirring for 30 min. The solid was collected by filtration, washed with 5 ml of 95% EtOH and dried under vacuum to give 1-[(4-chloro-6-methoxyquinolin-7-yloxy)methyl]-N-benzyloxycarbonyl-1-aminocyclopropane (273 mg; yield: 46%).

Workup

  1. customat 0° C.
  2. customfor 2 hours
  3. filtrationfiltered
  4. customto recover the unreacted 4-chloro-7-hydroxy-6-methoxyquinoline
  5. customThe filtrate was evaporated under vacuum
  6. additionthe resulting residue was added with 20 ml of 95% EtOH
  7. waitleft
  8. filtrationThe solid was collected by filtration
  9. washwashed with 5 ml of 95% EtOH
  10. customdried under vacuum

Sources & evidence

ORD record
ord-82728e9b44224145b1e5f3828220e06a
Source dataset
uspto-grants-2014_02
Patent number
US08642767B2

Reaction notes

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