Methanol → (R)-tert-Butyl 3-(tosyloxy)pyrrolidine-1-carboxylate

HRID 1916910Notes

Reaction equation

HRID 1916910 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[C:12]([N:19]1[CH2:23][CH2:22][C@@H:21]([OH:24])[CH2:20]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C(N(CC)CC)C.CO>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:15]([O:14][C:12]([N:19]1[CH2:23][CH2:22][C@@H:21]([O:24][S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=2)(=[O:9])=[O:8])[CH2:20]1)=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 887MethanolHCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 6544479tert-Butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 23560883(R)-tert-Butyl 3-(tosyloxy)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A round-bottomed flask was charged with p-toluenesulfonyl chloride (16.01 g, 83.98 mmol, 1.5 equiv.) and 150 ml of anhydrous DCM. The solution was cooled to an ice-water bath and evacuated and purged with nitrogen. To this solution was added a solution of (3R)-(−)-N—BOC-3-hydroxypyrrolidine (purchased from Aldrich) (10.47 g, 55.99 mmol) in 50 mL of DCM, followed by DMAP (0.66 g) and triethylamine (16.2 mL). The solution was stirred under nitrogen overnight from 0° C. to rt. TLC (5% MeOH in DCM) showed the completion of the reaction. The reaction was quenched by addition of polymer-supported amine (8 g), stirred 30 min. 100 mL of DCM was added. The organic layer was washed with H3PO4 (1M, 2×50 mL), followed by NaHCO3 (50 mL), brine (50 mL), dried (K2CO3), filtered through a silica gel pad, and concentrated to obtain the title compound as a liquid, 15.82 g (82.8%). MS: 363 (M+Na+); TLC (DCM) Rf=0.3.

Workup

  1. temperatureThe solution was cooled to an ice-water bath
  2. customevacuated
  3. custompurged with nitrogen
  4. customthe completion of the reaction
  5. customThe reaction was quenched by addition of polymer-supported amine (8 g)
  6. stirringstirred 30 min
  7. addition100 mL of DCM was added
  8. washThe organic layer was washed with H3PO4 (1M, 2×50 mL)
  9. dry with materialdried (K2CO3)
  10. filtrationfiltered through a silica gel pad
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-e962b327b4c44b6b8fac820553e86a5e
Source dataset
uspto-grants-2013_12
Patent number
US08618159B2

Reaction notes

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