2,4-Dichlorobenzyl chloride → (R)-2-[4-(2,4-Dichloro-benzyloxy)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1909722Notes

Reaction equation

HRID 1909722 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:22][C:23]1[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:24]=1[CH2:25]Cl.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:25][C:24]2[CH:27]=[CH:28][C:29]([Cl:31])=[CH:30][C:23]=2[Cl:22])=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 72122,4-Dichlorobenzyl chlorideHCID 10796Cesium carbonateHCID 68999591(R)-2-(4-Hydroxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68998876(R)-2-[4-(2,4-Dichloro-benzyloxy)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 57.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 25 mL vial which contained a solution of the product from step 1 (150 mg, 0.5 mmol) and 2,4-dichloro-benzyl chloride (180 mg, 0.8 mmol) in anhydrous DMF (15 mL) was added dry Cs2CO3 (150 mg, 0.75 mmol) at rt. The reaction mixture which resulted was allowed to stir at rt for 7 d. The mixture was poured onto 50 mL ice-water solution and extracted with EtOAc (3×30 mL) allowed). The combined organic layers were washed with water (30 mL) and brine (30 mL) and dried over anhy. Na2SO4. The solvent was removed under vacuo to obtain the crude product which was purified by silica gel flash chromatography to afford the title product (130 mg, 55%); 1H NMR (400 MHz, CDCl3); δ 1.47 (s, 9H), 1.80-2.10 (m, 4H), 3.26-3.45 (m, 2H), 3.69-3.91 (m, 1H), 4.01-4.18 (m, 2H), 5.07 (s, 2H), 6.84-6.90 (m, 4H), 7.25-7.28 (m, 1H), 7.41 (d, J=2.0 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H),

Workup

  1. customThe reaction mixture which resulted
  2. extractionextracted with EtOAc (3×30 mL)
  3. washThe combined organic layers were washed with water (30 mL) and brine (30 mL)
  4. customdried over anhy
  5. customThe solvent was removed under vacuo
  6. customto obtain the crude product which
  7. customwas purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-cd0a969aabb64aee95313352e84de690
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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