Triphenylphosphine → HCID 178498391, compound

HRID 525432Notes

Reaction equation

HRID 525432 reaction equation
[F:1][C:2]([F:26])([F:25])[CH:3]([N:15]1[CH2:20][CH2:19][CH:18]([C:21]([O:23][CH3:24])=[O:22])[CH2:17][CH2:16]1)[C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([OH:14])[CH:10]=2)[CH:5]=1.[C:27]([C@@H:31]1[CH2:36][CH2:35][C@H:34](O)[CH2:33][CH2:32]1)([CH3:30])([CH3:29])[CH3:28].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.C(OCC)(=O)C>[C:27]([C@H:31]1[CH2:36][CH2:35][C@H:34]([O:14][C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[CH:5]=[C:4]([CH:3]([N:15]2[CH2:20][CH2:19][CH:18]([C:21]([O:23][CH3:24])=[O:22])[CH2:17][CH2:16]2)[C:2]([F:1])([F:25])[F:26])[CH:13]=[CH:12]3)[CH2:33][CH2:32]1)([CH3:30])([CH3:29])[CH3:28]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 68279667Methyl 1-(2,2,2-trifluoro-1-(6-hydroxynaphthalen-2-yl)ethyl)piperidine-4-carboxylateHCID 178445811HCID 178445811, compound

Product 1

HCID 178498391HCID 178498391, compoundYield 32.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a stirring mixture of methyl 1-(2,2,2-trifluoro-1-(6-hydroxynaphthalen-2-yl)ethyl)piperidine-4-carboxylate (300 mg, 0.8 mmol), cis-4-(t-butyl)cyclohexanol (245 mg, 1.6 mmol, 2 eq) and PPh3 (420 mg, 1.6 mmol, 2 eq) in THF (3 mL) was added DIAD (323 g, 1.6 mmol, 2 eq) at room temperate under N2 atmosphere. The mixture was stirred at 80° C. for 2 h, diluted with ethyl acetate (10 mL) and washed with water (5 mL*3). The organic solvent was removed in vacuum and the residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=1:1) to give methyl 1-(1-(6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)-2,2,2-trifluoroethyl)piperidine-4-carboxylate (130 mg, yield: 31%) as a yellow solid. ESI-MS (M+1)+: 506.1. 1HNMR (400 MHz, CDCl3) δ: 7.86˜7.80 (m, 3H), 7.46 (d, J=8.8 Hz, 1H), 7.27 (s, 1H), 7.16 (d, J=8.8 Hz, 1H), 4.68˜4.66 (m, 1H), 4.39˜4.36 (m, 1H), 3.56 (s, 3H), 3.32˜3.30 (m, 2H), 2.65˜2.64 (m, 1H), 2.44-2.43 (m, 1H), 2.30-2.27 (m, 3H), 1.93-1.90 (m, 3H), 1.80-1.79 (m, 2H), 1.44˜1.41 (m, 2H), 1.29˜1.27 (m, 3H), 1.14˜1.13 (m, 1H), 0.90 (s, 9H).

Workup

  1. washwashed with water (5 mL*3)
  2. customThe organic solvent was removed in vacuum
  3. customthe residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-3c52170afdec4ccfafef8b98841f278c
Source dataset
uspto-grants-2016_05
Patent number
US09340527B2

Reaction notes

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