Dimethylformamide → (R)-methyl 1-(2-(((9H-fluoren-9-yl)methoxy)carbonyl)acetyl)-4,4-difluoropyrrolidine-2-carboxylate

HRID 1042887Notes

Reaction equation

HRID 1042887 reaction equation
C(NCC(O)=O)([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)C2C1=CC=CC=2)=O.N1(O)[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2N=N1.O[C:34]([C:36](F)(F)F)=[O:35].[CH3:40][O:41][C:42]([C@@H:44]1[CH2:48][C:47]([F:50])([F:49])[CH2:46][NH:45]1)=[O:43].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN([CH:90]=[O:91])C>C(Cl)Cl>[CH:26]1[C:31]2[CH:5]([CH2:4][O:3][C:90]([CH2:36][C:34]([N:45]3[CH2:46][C:47]([F:50])([F:49])[CH2:48][C@@H:44]3[C:42]([O:41][CH3:40])=[O:43])=[O:35])=[O:91])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:30]=2[CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 93124Fmoc-Gly-OHHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 668549754,4-Difluoro-L-proline methyl ester trifluoroacetate

Product 1

HCID 67318151(R)-methyl 1-(2-(((9H-fluoren-9-yl)methoxy)carbonyl)acetyl)-4,4-difluoropyrrolidine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A round bottom flask was charged with Fmoc-glycine (756 mg, 2543 μmol), 1H-benzo[d][1,2,3]triazol-1-ol (412 mg, 3052 μmol), (S)-methyl-4,4-difluoropyrrolidine-2-carboxylate TFA salt (710 mg, 2543 μmmol), Hunig's Base (2221 μl, 12717 μmol) and 10.2 mL DMF. The mixture was stirred for 5 min at RT, and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (1350 mg, 3052 μmol) was added. The reaction mixture was stirred overnight at RT. The solution was diluted with DCM and washed with water. The organic layer was dried, filtered, and concentrated. The crude oil was purified by silica gel chromatography, 0-5% MeOH/DCM to provide (R)-methyl 1-(2-(((9H-fluoren-9-yl)methoxy)carbonyl)acetyl)-4,4-difluoropyrrolidine-2-carboxylate. MS: [M+H]=445.

Workup

  1. stirringThe reaction mixture was stirred overnight at RT
  2. washwashed with water
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude oil was purified by silica gel chromatography, 0-5% MeOH/DCM

Sources & evidence

ORD record
ord-ee1e559141f34ee792a5ff7834c5c873
Source dataset
uspto-grants-2013_10
Patent number
US08557816B2

Reaction notes

Loading…