Triphenylphosphine → Methyl 2-(1-tert-Butoxycarbonylpiperidin-4-yloxy)-4-fluorobenzoate

HRID 1787889Notes

Reaction equation

HRID 1787889 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([OH:12])[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][CH:42](O)[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl.C1C=CC=CC=1>[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][CH:42]([O:12][C:4]2[CH:3]=[C:2]([F:1])[CH:11]=[CH:10][C:5]=2[C:6]([O:8][CH3:9])=[O:7])[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:33])[CH3:34]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 2775386Methyl 4-fluorosalicylate

Product 1

HCID 57602502Methyl 2-(1-tert-Butoxycarbonylpiperidin-4-yloxy)-4-fluorobenzoateYield 61%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of methyl 4-fluoro-2-hydroxybenzoate (5.1 g, 30 mmol), triphenylphosphine (9.5 g, 36 mmol), 1-tert-butoxycarbonyl-4-hydroxypiperidine (6 g, 30 mmol), and benzene (10 mL) was heated until all solids dissolved. The solution was cooled to 0° C., then sonicated while adding diethyl azodicarboxylate (6.3 g, 36 mmol) dropwise. After the addition was complete, the reaction mixture was sonicated for an additional 60 min, diluted with CH2Cl2 (25 mL), and purified by flash chromatography, eluting with 10% EtOAc in hexanes to yield the title compound (6.45 g, 61%) as a white solid.

Workup

  1. temperaturewas heated until all solids
  2. dissolutiondissolved
  3. customsonicated
  4. additionAfter the addition
  5. customthe reaction mixture was sonicated for an additional 60 min
  6. custompurified by flash chromatography
  7. washeluting with 10% EtOAc in hexanes

Sources & evidence

ORD record
ord-5b54b93e44bc459fb114f8396288f7b7
Source dataset
uspto-grants-2009_03
Patent number
US07511066B2

Reaction notes

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