Acetic Acid → 1-(3-chloro-4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl ester

HRID 2374419Notes

Reaction equation

HRID 2374419 reaction equation
C([BH3-])#N.[Na+].[CH2:5]([O:8][C:9]([C:11]1[N:12]([NH2:16])[CH:13]=[CH:14][CH:15]=1)=[O:10])[CH:6]=[CH2:7].[Cl:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[F:26])[CH:21]=O.C(O)(=O)C>CO>[CH2:5]([O:8][C:9]([C:11]1[N:12]([NH:16][CH2:21][C:20]2[CH:23]=[CH:24][C:25]([F:26])=[C:18]([Cl:17])[CH:19]=2)[CH:13]=[CH:14][CH:15]=1)=[O:10])[CH:6]=[CH2:7]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5938663-Chloro-4-fluorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 598535721-amino-1H-pyrrole-2-carboxylic acid allyl ester

Product 1

HCID 598536021-(3-chloro-4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl esterYield 65.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

Sodium cyanoborohydride (1.11 g, 16.8 mmol) was added to a solution of 1-amino-1H-pyrrole-2-carboxylic acid allyl ester (Example 1b, 1.12 g, 6.74 mmol), 3-chloro-4-fluorobenzaldehyde (1.32 g, 8.08 mmol) and acetic acid (1.2 mL), in methanol (50 mL) at 25° C. The reaction mixture was stirred at 25° C. for 18 h, quenched with saturated aqueous sodium bicarbonate solution and was extracted with ethyl acetate (2×50 mL). The organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. Purification of the residue by flash column chromatography (Teledyne Isco RediSep 40 g, 0→40% ethyl acetate in hexanes) afforded the desired product, 1-(3-chloro-4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl ester (1.36 g, 4.41 mmol, 65% yield) as an off-white oil. 1H NMR (400 MHz, CDCl3) δ 4.06 (2H, d, J=5.5 Hz), 4.76 (2H, d, J=5.3 Hz), 5.29 (1H, d, J=11.0 Hz), 5.40 (1H, d, J=16.4 Hz), 5.96-6.05 (2H, m), 6.58 (1H, t, J=5.5 Hz), 6.76 1H, (t, J=1.9 Hz), 6.91 (1H, dd, J1=4.3 Hz, J2=1.8 Hz), 7.06 (1H, t, J=8.6 Hz), 7.10-7.14 (1H, m), 7.33 (1H, dd, J1=7.1 Hz, J2=1.4 Hz).

Workup

  1. customquenched with saturated aqueous sodium bicarbonate solution
  2. extractionwas extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by flash column chromatography (Teledyne Isco RediSep 40 g, 0→40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-8aeb22c0528f4b44820b448bc44b36d1
Source dataset
uspto-grants-2008_12
Patent number
US07462611B2

Reaction notes

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