Dichloromethane → (trans)-Naphthalen-2-ylmethyl 3-fluoro-4-hydroxypyrrolidine-1-carboxylate

HRID 1095748Notes

Reaction equation

HRID 1095748 reaction equation
[CH:1]12[O:6][CH:5]1[CH2:4][N:3]([C:7]([O:9][CH2:10][C:11]1[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=1)=[O:8])[CH2:2]2.C1C=CN=CC=1.[FH:27].C(Cl)Cl>>[F:27][C@H:1]1[C@H:5]([OH:6])[CH2:4][N:3]([C:7]([O:9][CH2:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=2)=[O:8])[CH2:2]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 64774Pyridine, hydrofluoride (1:1)HCID 86638608Naphthalen-2-ylmethyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate

Product 1

HCID 131729524(trans)-Naphthalen-2-ylmethyl 3-fluoro-4-hydroxypyrrolidine-1-carboxylateYield 23.3%

Procedure

A plastic (HDPE) bottle was charged with naphthalen-2-ylmethyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate (945 mg, 3.509 mmol) and HF-pyridine (264 μL, 10.527 mmol) in DCM (17.55 ml, 3.509 mmol) and the reaction mixture was stirred for 36 hours at ambient temperature. The reaction was slowly quenched with aqueous saturated NaHCO3 and diluted with water and DCM. The reaction mixture was extracted with DCM, and the combined organics layers were dried over Na2SO4 and concentrated to give the product as an oil (237 mg, 23.3% yield)

Workup

  1. customThe reaction was slowly quenched with aqueous saturated NaHCO3
  2. additiondiluted with water and DCM
  3. extractionThe reaction mixture was extracted with DCM
  4. dry with materialthe combined organics layers were dried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-db29f44b12e44ffaa36946fb442d8521
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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