Triethylamine → Methyl-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-methylbenzoate

HRID 350360Notes

Reaction equation

HRID 350360 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18](I)=[CH:17][C:16]=1[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC>CS(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:5][C:6](=[O:7])[C:18]1[CH:19]=[CH:20][C:15]([O:14][CH2:13][CH:9]2[CH2:10][CH2:11][CH2:12][N:8]2[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[C:16]([CH3:22])[CH:17]=1

Participants

6

Reactant 2

HCID 8471TriethylamineHCID 235124474-[1-(Tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-1-iodo-3-methylbenzene

Product 1

HCID 23512098Methyl-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-methylbenzoateYield 111.7%

Reagents, catalysts & solvents 3

HCID 812191,3-Bis(diphenylphosphino)propaneCatalystHCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-1iodo-3-methylbenzene (645.3 mg, 1.546 mmol) in DMSO (7 mL) and MEOH (6 mL) was added Et3N (0.47 mL, 3.401 mmol), Pd(OAc)2 (17.4 mg, 0.077 mmol) and 1,3-bis(diphenylphosphino) propane (31.46 mg, 0.077 mmol). To the stirred mixture was induced CO gas for 10 min. The mixture was stirred at 70° C. for 2 days and concentrated. The residue was diluted with EtOAc, washed with brine, and dried over Na2SO4. The solvent was removed under a reduced pressure, and the residue was chromatographed on silica-gel with n-hexane-EtOAc (5:1, v/v) as eluent to afford 301.6 mg (56%) methyl4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-methylbenzoate as an oil. 1H-NMR (400 MHz, CDCl3) δ 1.47 (s, 9H), 1.86–2.10 (br m, 4H), 2.33 (s, 3H), 3.32–3.50 (br m, 2H), 3.88 (s, 3H), 3.88, 4.04 (br m each, 1H), 4.13–4.20 (m, 2H), 6.89 (br m, 1H), 7.82 (s, 1H), 7.85 (dd, J=2.0, 8.8 Hz, 1H); MS (FAB) m/z 350 (M++1).

Workup

  1. customfor 10 min
  2. concentrationconcentrated
  3. additionThe residue was diluted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed under a reduced pressure
  7. customthe residue was chromatographed on silica-gel with n-hexane-EtOAc (5:1

Sources & evidence

ORD record
ord-293102e0fc3544a4ba4dd455d2e22b8d
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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