Pyrrolidine → 2-Chloro-3-(1-pyrrolidinylmethyl)phenol

HRID 1159418Notes

Reaction equation

HRID 1159418 reaction equation
[Cl:1][C:2]1[C:9]([OH:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[NH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].OS([O-])(=O)=O.[Na+]>C(Cl)Cl.O>[Cl:1][C:2]1[C:3]([CH2:4][N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:6][CH:7]=[CH:8][C:9]=1[OH:10]

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 516919Sodium BisulfateHCID 5933762-Chloro-3-hydroxybenzaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 686199382-Chloro-3-(1-pyrrolidinylmethyl)phenolYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

2-Chloro-3-hydroxybenzaldehyde (4.5 g, 0.03 mol) was added in portions for 30 min to a mixture of pyrrolidine (3. mL, 0.036 mol) and NaB(OAc)3H (7.6 g, 0.036 mol) in CH2Cl2 (50 mL) under vigorous stirring and cooling with an ice bath in an atmosphere of argon. The mixture was stirred for 3 h and cooled with an ice bath. Water (50 mL) and 5N NaHSO4 (to pH 1) were added. The organic layer was separated and discarded. The aqueous one was alkalized with saturated K2CO3 to pH 6 and extracted with chloroform (2×50 mL). The combined extracts were dried with Na2SO4, and evaporated to give the title compound (5.76 g, 95%) as white crystals. LCMS-data: (M+H)+ 214.0 and 212.0 (calculated for C11H14ClNO 211.7). 1H NMR data (DMSO-d6): 9.95 (br. s, 1H, ArOH), 7.07 (t, 1H, J1=7.8 Hz, J2=15.7, Ar—H), 6.90 (dd, 1H, J1=1.5 Hz, J2=7.6 Hz, Ar—H); 6.85 (dd, 1H, J1=1.5, J2=9.5, Ar—H), 3.63 (s, 2H, ArCH2), 2.43-2.50 (m, 4H, pyrrolidine (CH2)2N), 1.63-1.73 (m, 4H, CH2CH2CH2CH2).

Workup

  1. temperaturecooling with an ice bath in an atmosphere of argon
  2. stirringThe mixture was stirred for 3 h
  3. temperaturecooled with an ice bath
  4. customThe organic layer was separated
  5. extractionextracted with chloroform (2×50 mL)
  6. dry with materialThe combined extracts were dried with Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-5caaa691217d4e53b0d6bb94c98cfc6b
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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