Trifluoroacetic acid → HCID 58641321, compound

HRID 1394936Notes

Reaction equation

HRID 1394936 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14](OC(C)(C)C)=[O:15])[C@:11]([CH3:27])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:10]=1.O[C@@H]1[CH2:33][N:32](C(OC(C)(C)C)=O)[C@:31](C)(C2C=CC=CC=2)C1.FC(F)(F)C(O)=O.C(N(CC)CC)C.CN(C)C(Cl)=O>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([N:32]([CH3:33])[CH3:31])=[O:15])[C@:11]([CH3:27])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:10]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 58641182HCID 58641182, compoundHCID 58641194HCID 58641194, compound

Product 1

HCID 58641321HCID 58641321, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl(2S)-4-(2,5-difluorophenyl)-2-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate (21-3, prepared from tert-butyl(2S,4S)-4-hydroxy-2-methyl-2-phenylpyrrolidine-1-carboxylate (21-2) by the procedures of Scheme 20, 24 mg, 0.065 mmol, 1 equiv) in a 1:1 mixture of trifluoroacetic acid and dichloromethane (10 mL) was stirred for 30 minutes, then concentrated. The residue was dried via toluene azeotrope (2×10 mL), then dissolved in dichloromethane (10 mL). Triethylamine (0.090 mL, 0.65 mmol, 10 equiv) and dimethylcarbamoyl chloride (0.030 mL, 0.33 mmol, 5.0 equiv) were added, and the resulting mixture was stirred at 40° C. for 6 hours, then 23° C. for 2 days. The reaction mixture was partitioned between aqueous saturated sodium bicarbonate solution (30 mL) and ethyl acetate (2×25 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (hexanes initially, grading to 40% ethyl acetate in hexanes) to provide (2S)-4-(2,5-difluorophenyl)-N,N,2-trimethyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (21-4) as an off-white solid. 1H NMR (500 MD, CDCl3) δ 7.40 (br d, 2H, J=7.7 Hz), 7.32 (br t, 2H, J=7.8 Hz), 7.22 (t, 1H, J=7.5 Hz), 7.08-6.91 (m, 3H), 6.24 (m, 1H), 4.82 (dd, 1H, J=13.9, 1.5 Hz), 4.77 (dd, 1H, J=13.9, 1.5 Hz), 2.77 (s, 6H), 2.02 (s, 3H). LRMS m/z (M+H) 343.0 found, 343.2 required.

Workup

  1. concentrationconcentrated
  2. dry with materialThe residue was dried via toluene
  3. dissolutiondissolved in dichloromethane (10 mL)
  4. stirringthe resulting mixture was stirred at 40° C. for 6 hours
  5. wait23° C. for 2 days
  6. customThe reaction mixture was partitioned between aqueous saturated sodium bicarbonate solution (30 mL) and ethyl acetate (2×25 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography (hexanes initially

Sources & evidence

ORD record
ord-558177599fc943b59758a44925e71cf4
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

Loading…