4-Hydroxybenzaldehyde → 4-(Pyrrolidin-1-ylmethyl)phenol

HRID 1159410Notes

Reaction equation

HRID 1159410 reaction equation
[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[NH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1.[OH:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=1.Cl>C(Cl)Cl>[N:15]1([CH2:25][C:24]2[CH:27]=[CH:28][C:21]([OH:20])=[CH:22][CH:23]=2)[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 1264-HydroxybenzaldehydeHCID 313Hydrochloric AcidHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 187719784-(Pyrrolidin-1-ylmethyl)phenolYield 98.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

NaB(OAc)3H (32 g, 0.15 mol) was added in portions for 15 min to a mixture of pyrrolidine (9.1 mL, 0.11 mol) and 4-hydroxybenzaldehyde (12.2 g, 0.1 mol) in CH2Cl2 (100 mL) under vigorous stirring and cooling with an ice bath in an atmosphere of argon Ar. The mixture was stirred for 20 h and cooled with an ice bath. Concentrated HCl (20 mL) was added. The organic layer was separated and discarded. The aqueous one was alkalized with K2CO3 to pH 9 (40 mL) and extracted with chloroform (3×100 mL). The combined extracts were dried with Na2SO4, and evaporated to give the title compound (17.4 g, 98%) was obtained as white crystals. LCMS-data: (M+H)+ 178.1 and 179.1 (calculated for C11H15NO 177.0). 1H NMR (400Mz)-data (DMSO-d6, J, Hz): 9.19 (br s, 1H, OH); 7.03-7.11 (t, 1H, ArH, J=7.5 Hz); 6.66-6.73 (m, 1H, ArH); 6.34-6.59 (dd, 1H, ArH, J1=1.7 Hz, J2=6.4 Hz); 3.46 (s, 2H, CH2Ar); 2.37-2.43 (m, 4H, CH2CH2CH2CH2); 1.62-1.73 (m, 4H, CH2CH2CH2CH2).

Workup

  1. temperaturecooling with an ice bath in an atmosphere of argon Ar
  2. stirringThe mixture was stirred for 20 h
  3. temperaturecooled with an ice bath
  4. customThe organic layer was separated
  5. extractionextracted with chloroform (3×100 mL)
  6. dry with materialThe combined extracts were dried with Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-06a7692029e4492cbfa7d0cd6be2d7f7
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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