Triphenylphosphine → 1-Bromo-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzene

HRID 350368Notes

Reaction equation

HRID 350368 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.[C:10]([O:14][C:15]([N:17]1[CH2:23][CH2:22][CH2:21][C@H:18]1[CH2:19]O)=[O:16])([CH3:13])([CH3:12])[CH3:11].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>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:19][CH:18]2[CH2:21][CH2:22][CH2:23][N:17]2[C:15]([O:14][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:16])=[C:4]([F:9])[CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 643448(S)-(-)-N-Boc-prolinolHCID 27249814-Bromo-2-fluorophenolHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 235119311-Bromo-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzeneYield 73.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-bromo-2-fluorophenol (217 ul, 2.002 mmol), N-tert-butoxycarbonyl prolinol (403 mg, 2.002 mmol), and Ph3P (630 mg, 2.403 mmol) in THF (7 mL) was added DIAD (477 ul, 2.423 mmol) at room temp. The resulting mixture was stirred for 6 hr at room temp and then overnight at 70° C. The mixture was concentrated in vacuo and the residue was chromatographed on silica-gel with n-hexane-EtOAc (5:1, v/v) as eluent to give 549.4 mg (73%) 1-bromo-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzene as an oil. 1H-NMR (400 MHz, CDCl3) δ 1.46 (s, 9H), 1.85 (br m, 1H), 1.90–2.10 (br s, 3H), 3.30–3.47 (m, 2H), 3.85, 4.04 (br s each, 1H), 4.11–4.20 (m, 2H), 6.82–6.98 (m, 1H), 7.13–7.26 (m, 2H); MS (FAB) m/z 374 (M++1).

Workup

  1. customovernight
  2. customat 70° C
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue was chromatographed on silica-gel with n-hexane-EtOAc (5:1

Sources & evidence

ORD record
ord-d265da1504814f138896b42e64a802e6
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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