Sodium Carbonate → 3-(3-Chloro-5-fluorophenyl)-1-methylpyrrolidin-3-ol

HRID 1931816Notes

Reaction equation

HRID 1931816 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:14])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[C:15](=O)([O-])[O-].[Na+].[Na+]>C(O)=O.C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:14])[CH2:13][CH2:12][N:11]([CH3:15])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 2

HCID 10340Sodium CarbonateHCID 685156533-(3-Chloro-5-fluorophenyl)pyrrolidin-3-ol

Product 1

HCID 251438123-(3-Chloro-5-fluorophenyl)-1-methylpyrrolidin-3-ol

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 712FormaldehydeSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-(3-chloro-5-fluorophenyl)pyrrolidin-3-ol (0.4 g, 1.85 mmol) in formic acid (5.4 mL) and aqueous formaldehyde (40%, 4.8 mL) was heated at 85° C. for 2.5 h. Aqueous sodium carbonate (10%, 50 mL) was added and the aqueous phase was extracted with ethyl acetate (2×70 mL), the combined organic phase was dried (MgSO4) and evaporated. Purification by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 20:80 to 100:0) gave the title compound (0.131 g). The amine was converted to the fumaric acid salt and recrystallized from methanol/diethyl ether/diisopropyl ether: M.p. 129-131° C.; MS m/z (relative intensity, 70 eV) 229 (M+, 7), 157 (5), 129 (6), 58 (30), 57 (bp).

Workup

  1. extractionthe aqueous phase was extracted with ethyl acetate (2×70 mL)
  2. dry with materialthe combined organic phase was dried (MgSO4)
  3. customevaporated
  4. customPurification by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 20:80 to 100:0)

Sources & evidence

ORD record
ord-554aa17379804084aef6bfb5a637c445
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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