1,3-Bis(diphenylphosphino)propane → Methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoate

HRID 350369Notes

Reaction equation

HRID 350369 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[C:4]([F:22])[CH:3]=1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CS(C)=O.CO.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:18]([O:17][C:15]([N:11]1[CH2:12][CH2:13][CH2:14][CH:10]1[CH2:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([C:15]([O:17][CH3:18])=[O:16])=[CH:3][C:4]=1[F:22])=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 2

HCID 812191,3-Bis(diphenylphosphino)propaneHCID 235119311-Bromo-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzene

Product 1

HCID 23512180Methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoateYield 124.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 1-bromo4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzene (549.4 mg, 1.468 mmol) in DMSO (6 mL) and MeOH (5 mL) was added Et3 N (448 ul, 3.229 mmol), Pd(OAc)2 (36.2 mg, 0.161 mmol), and 1,3-bis(diphenylphosphino)propane (66.4 mg, 0.161 mmol). To the mixture was induced CO gas for 10 min. The resulting mixture was stirred at 70° C. for 2 days under a current of CO. After the mixture was concentrated, the residue was diluted with EtOAc. The solution was washed with brine and dried over Na2SO4. The solvent was removed under a reduced pressure and the residue was chromatographed on silica-gel eluting with n-hexane:EtOAc (5:1, v/v) as eluent to afford 323.0 mg (62%) methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoate as a pale yellow oil. 1H-NMR (400 MHz, CDCl3) δ 1.47 (s, 9H), 1.87 (br s, 1H), 1.95–2.10 (m, 3H), 3.34–3.44 (br m, 2H), 3.89 (s, 3H), 3.94 and 4.11–4.26 (br m each, 3H), 7.03–7.11 (m, 1H), 7.75–7.80 (m, 2H); MS (FAB) m/z 354 M++1).

Workup

  1. customfor 10 min
  2. concentrationAfter the mixture was concentrated
  3. additionthe residue was diluted with EtOAc
  4. washThe solution was washed 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
  8. washeluting with n-hexane:EtOAc (5:1

Sources & evidence

ORD record
ord-4102c1ab981c47a28d0893bc320fa521
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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