Hydrochloric Acid → 2-Methoxy-6-chloro-4-(pyrrolidin-1-ylmethyl)phenol

HRID 1159411Notes

Reaction equation

HRID 1159411 reaction equation
[BH-](OC(C)=O)(OC(C)=O)[O:2][C:3](C)=O.[Na+].[NH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1.CO[C:22]1[CH:29]=[C:28]([OH:30])[C:27]([Cl:31])=[CH:26][C:23]=1[CH:24]=O.Cl>C(Cl)Cl>[CH3:3][O:2][C:29]1[CH:22]=[C:23]([CH2:24][N:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:26]=[C:27]([Cl:31])[C:28]=1[OH:30]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 866303945-Chloro-4-hydroxy-2-methoxybenzaldehyde

Product 1

HCID 686208132-Methoxy-6-chloro-4-(pyrrolidin-1-ylmethyl)phenolYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

NaB(OAc)3H (12.5 g, 0.098 mol) was added in portions for 15 min to a mixture of pyrrolidine (5.41 mL, 0.087 mol) and 2-methoxy-5-chloro-4-hydroxybenzaldehyde (12.5 g, 0.089 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 (18 mL) was added. The organic layer was separated and discarded. The aqueous one was alkalized with 10 N NaOH to pH 9 (30 mL) and extracted with chloroform (2×100 mL). The combined extracts were dried with Na2SO4, and evaporated to give compound (5.1 g, 75%) was obtained as white crystals. LCMS-data: 242.0 (M+H)+, (calculated for C12H16NOCl 241.5). 1H NMR (400 MHz)-data (DMSO-d6, J, Hz): 9.18 (br s, 1H, OH); 6.83 (s, 2H, ArH); 3.79 (s, 3H, CH3); 3.44 (s, 2H, CH2Ar); 2.36-2.44 (m, 4H, CH2CH2CH2CH2,); 1.65-1.72 (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 (2×100 mL)
  6. dry with materialThe combined extracts were dried with Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-831aa7ddc11a4c24acf4ab4fca79c459
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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