Potassium Carbonate → 2,4-Dichloro-3-(pyrrolidin-1-ylmethyl)phenol

HRID 1159378Notes

Reaction equation

HRID 1159378 reaction equation
[Cl:1][C:2]1[C:9]([OH:10])=[CH:8][CH:7]=[C:6]([Cl:11])[C:3]=1[CH:4]=O.[NH:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])([O-])=O.[K+].[K+]>ClCCl.O>[Cl:1][C:2]1[C:3]([CH2:4][N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[C:6]([Cl:11])[CH:7]=[CH:8][C:9]=1[OH:10]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 104425302,6-Dichloro-3-hydroxy-benzaldehyde

Product 1

HCID 686208052,4-Dichloro-3-(pyrrolidin-1-ylmethyl)phenolYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of intermediate 22, 2,6-Dichloro-3-hydroxybenzaldehyde (5.00 g, 26.18 mmol) in 5 mL of dichloromethane was added to a mixture of pyrrolidine (2.75 mL, 32.72 mmol) and sodium triacetoxyborohydride (6.94 g, 32.72 mmol) in dichloromethane (45 mL) under stirring. The reaction mixture was stirred for 16 h at room temperature. Water (20 mL) and saturated K2CO3 (5 mL) were added, and the layers were separated. The water layer was subjected to extraction with CHCl3 (2×50 mL). The combined organic layers were washed with water (30 mL), brine, dried with Na2SO4, and evaporated. The residue was purified by chromatography (silica gel, 63/100 μm, 50 g, CHCl3/MeOH 100:0→80:20). Fractions containing the target compound were evaporated. The residue was crystallized from ether to furnish the title compound (4.7 g, 73%) as white crystals. LCMS data: 246 and 248 (M+H)+ (calculated for C11H13Cl2NO 246.14). 1H NMR data (DMSO-d6): 10.47 (br.s, 1H, OH); 7.19 (d, 1H, J=9 Hz, Ar—H); 6.89 (d, 1H, J=9 Hz, Ar—H); 3.78 (s, 2H, CH2Ar); 2.50-2.56 (m, 4H, CH2NCH2); 1.60-1.68 (m, 4H, CH2CH2).

Workup

  1. stirringThe reaction mixture was stirred for 16 h at room temperature
  2. customthe layers were separated
  3. extractionThe water layer was subjected to extraction with CHCl3 (2×50 mL)
  4. washThe combined organic layers were washed with water (30 mL), brine
  5. dry with materialdried with Na2SO4
  6. customevaporated
  7. customThe residue was purified by chromatography (silica gel, 63/100 μm, 50 g, CHCl3/MeOH 100:0→80:20)
  8. additionFractions containing the target compound
  9. customwere evaporated
  10. customThe residue was crystallized from ether

Sources & evidence

ORD record
ord-74a33e535403444f88de13b091309b5d
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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