Triphenylphosphine → HCID 16093629, compound

HRID 350350Notes

Reaction equation

HRID 350350 reaction equation
[OH:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1[O:13][CH3:14].[C:15]([N:22]1[CH2:28][CH2:27][CH2:26][C@H:23]1[CH2:24]O)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].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>[CH3:14][O:13][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:2]=1[O:1][CH2:24][C@@H:23]1[CH2:26][CH2:27][CH2:28][N:22]1[C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[C:6]([O:8][CH2:9][CH3:10])=[O:7]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 12038Ethyl vanillateHCID 643448(S)-(-)-N-Boc-prolinolHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 16093629HCID 16093629, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 4-hydroxy-3-methoxybenzoate (3.00 g, 15.29 mmol), (S)-N-Boc-prolinol (3.08 g, 15.30 mmol), Ph3P (4.81 g, 18.34 mmol) in THF (50 mL) was added DIAD (3.61 mL, 18.33 mmol) at 0° C. The resulting mixture was heated under reflux 6.5 hr. After cooling to room temp, the mixture was evaporated and purified by column chromatography on silica-gel with CHCl3-MeOH (50:1, v/v) as eluent to give ethyl (S)-3-methoxy-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl methoxy]benzoate as a gum. The above ethyl (S)-3-methoxy-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinylmethoxy]benzoate was dissolved in CH2Cl2 (50 mL) and TFA (45 mL). The mixture was stirred for 2 days at room temp. The resulting mixture was concentrated in vacuo and made basic with sat. NaHCO3. The mixture was extracted with CH2Cl2, washed with brine, and dried over MgSO4. The solvent was evaporated and the residue was purified by column chromatography on silica-gel with CHCl3-MeOH (20:1, v/v) as eluent to give 3.27 g (77% for 2 steps) ethyl (S)-3-methoxy-4-(2-pyrrolidinylmethoxy) benzoate as a yellow oil. 1H-NMR (CDCl3) δ 1.39 (t, 3 H, J=7.1 Hz), 1.52–1.59 (m, 1 H), 1.76–1.88 (m, 2 H), 1.92–2.01 (m, 1H), 2.92–3.06 (m, 2 H), 3.56–3.63 (m, 1 H), 3.90 (s, 3 H), 3.91–4.02 (m, 2 H), 4.35 (q, 2 H, J=7.1 Hz), 6.89 (d, 1 H, J=8.3 Hz), 7.54 (d, 1 H, J=2.0 Hz), 7.65 (dd, 1 H, J=2.0, 8.3 Hz).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux 6.5 hr
  3. customthe mixture was evaporated
  4. custompurified by column chromatography on silica-gel with CHCl3-MeOH (50:1

Sources & evidence

ORD record
ord-53b7f1a5a2ee4df3a7383851bb8d7d86
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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