Triethylamine → [4-(4-{[1-(Benzyloxycarbonyl)cyclopropanecarbonyl]amino}phenoxy)-3-fluoropyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

HRID 2265614Notes

Reaction equation

HRID 2265614 reaction equation
[C:1]1([O:7][C:8](=[O:34])[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH2:32])=[C:28](F)[CH:27]=3)[CH:22]=[CH:21][N:20]=2)[C:10]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:35]([O:42][C:43]([C:45]1([C:48]([OH:50])=O)[CH2:47][CH2:46]1)=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(N(CC)CC)C.[F:58][P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[C:1]1([O:7][C:8](=[O:34])[N:9]([C:19]2[C:24]([F:58])=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:48]([C:45]4([C:43]([O:42][CH2:35][C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[O:44])[CH2:47][CH2:46]4)=[O:50])=[CH:28][CH:27]=3)[CH:22]=[CH:21][N:20]=2)[C:10]([O:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:11])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 574708601-(Benzyloxycarbonyl)cyclopropanecarboxylic acidHCID 67136032[4-(4-amino-3-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

Product 1

HCID 68686952[4-(4-{[1-(Benzyloxycarbonyl)cyclopropanecarbonyl]amino}phenoxy)-3-fluoropyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A crude product of [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (678 mg) was dissolved in N,N-dimethylformamide (25 ml). 1-(benzyloxycarbonyl)cyclopropanecarboxylic acid (815 mg), triethylamine (0.516 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.64 g) were added under a nitrogen atmosphere at room temperature, followed by stirring overnight. Liquid-liquid separation was carried out after addition of ethyl acetate and water to the reaction mixture. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (3 times) and brine in this order, and dried over anhydrous sodium sulfate. The solvent was removed, and the resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=2:1) to provide the titled compound as a colorless oil (928 mg).

Workup

  1. customLiquid-liquid separation
  2. additionafter addition of ethyl acetate and water to the reaction mixture
  3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (3 times) and brine in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed
  6. customthe resultant residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-97e5bb0d25e94f70af80bea99b3adeba
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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