Pyrrolidine → HCID 67278673, compound

HRID 1694424Notes

Reaction equation

HRID 1694424 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Br:20][C:21]1[CH:28]=[C:27]([F:29])[C:24]([CH:25]=O)=[C:23]([F:30])[CH:22]=1.OS([O-])(=O)=O.[Na+]>ClCCl.O>[Br:20][C:21]1[CH:28]=[C:27]([F:29])[C:24]([CH2:25][N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[C:23]([F:30])[CH:22]=1

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 516919Sodium BisulfateHCID 27732904-Bromo-2,6-difluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 67278673HCID 67278673, compoundYield 79.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Pyrrolidine (25 mL, 0.30 mol) and sodium triacetoxyborohydride (64 g, 0.30 mol) were added in portions to a stirred solution of Intermediate 18a, 4-Bromo-2,6-difluorobenzaldehyde (53.5 g, 0.24 mol) in dichloromethane (500 mL) on ice bath. The reaction mixture was intensively stirred for 12 h at RT. Water (400 mL) was added followed by addition of 5M aq. NaHSO4 to attain pH˜2. The organic layer was separated. The aqueous one was extracted with CH2Cl2 (2×200 mL). The organic layers were discarded. The aqueous fraction was alkalized with K2CO3 to pH˜10, and extracted with CHCl3 (2×300 mL). The organic extract was washed with brine, dried over anhydrous Na2SO4 (100 g) and evaporated in vacuo to give the title compound (52.5 g, 79%, 0.19 mol). LC/MS data: 275.9 and 277.9 (M+H)+ (calculated for C11H12BrF2N, 276.13). 1H NMR data (DMSO-d6): 7.40-7.48 (m, 2H Ar—H), 3.66 (s, 2H, Ar—CH2), 2.38-2.46 (m, 4H pyrrolidine (CH2)2N), 1.61-1.71 (m, 4H, CH2CH2CH2CH2).

Workup

  1. customThe organic layer was separated
  2. extractionThe aqueous one was extracted with CH2Cl2 (2×200 mL)
  3. extractionextracted with CHCl3 (2×300 mL)
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous Na2SO4 (100 g)
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-20c6ad33d26244cdb0731d0670d33b1d
Source dataset
uspto-grants-2012_04
Patent number
US08158673B2

Reaction notes

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