Pyrrolidine → 3-Methyl-4-(pyrrolidin-1-ylmethyl)phenol

HRID 1159417

Reaction equation

HRID 1159417 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([CH3:10])[CH:3]=1.[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>[CH3:10][C:4]1[CH:3]=[C:2]([OH:1])[CH:9]=[CH:8][C:5]=1[CH2:6][N:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 4581854-Hydroxy-2-methylbenzaldehydeHCID 516919Sodium BisulfateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 686199283-Methyl-4-(pyrrolidin-1-ylmethyl)phenolYield 94.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

4-Hydroxy-2-methylbenzaldehyde (1.1 g, 8 mmol) was added in portions for 30 min to a mixture of pyrrolidine (0.84 mL, 10 mmol) and NaB(OAc)3H (2.14 g, 10 mmol) in CH2Cl2 (10 mL) under vigorous stirring and cooling with an ice bath in an atmosphere of argon. The mixture was stirred for 12 h and cooled with an ice bath. Water (20 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 (2×25 mL). The combined extracts were dried with Na2SO4, and evaporated to give the title compound (1.45 g, 94%) was obtained as dark-yellow crystals. LCMS-data: (M+H)+ 193.1 and 192.1 (calculated for C12H17NO 191.3). 1H NMR data (DMSO-d6): 9.08 (br. s, 1H ArOH), 6.97 (d, 1H, J=8.1 Hz, Ar—H), 6.54 (d, 1H, J=2.4 Hz, Ar—H); 6.49 (dd, 1H, J1=2.4 Hz, J2=8.1 Hz, Ar—H), 3.40 (s, 2H, ArCH2), 2.33-2.45 (m, 4H, pyrrolidine (CH2)2N),), 2.21 (s, 3H, OCH3), 1.60-1.68 (m, 4H, CH2CH2CH2CH2).

Workup

  1. temperaturecooling with an ice bath in an atmosphere of argon
  2. stirringThe mixture was stirred for 12 h
  3. temperaturecooled with an ice bath
  4. customThe organic layer was separated
  5. extractionextracted with chloroform (2×25 mL)
  6. dry with materialThe combined extracts were dried with Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-09321d21e421469b9219d218e93c6239
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Linked notes

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