2,6-Lutidine → 2-(3-(R)-t-Butydimethylsilyloxymethyl-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)-3-ethylvaleric Acid, 4-methoxybenzyl Ester

HRID 1068244Notes

Reaction equation

HRID 1068244 reaction equation
[CH2:1]([CH:3]([CH2:18][CH3:19])[CH:4](O)[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)=[O:6])[CH3:2].FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.N1C(C)=CC=CC=1C.CCN(C(C)C)C(C)C.[Si:52]([O:59][CH2:60][C@@H:61]1[C@@H:65]([C:66]2[CH:71]=[CH:70][CH:69]=[C:68]([F:72])[CH:67]=2)[CH2:64][NH:63][CH2:62]1)([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53]>C(Cl)Cl>[Si:52]([O:59][CH2:60][C@@H:61]1[C@@H:65]([C:66]2[CH:71]=[CH:70][CH:69]=[C:68]([F:72])[CH:67]=2)[CH2:64][N:63]([CH:4]([CH:3]([CH2:18][CH3:19])[CH2:1][CH3:2])[C:5]([O:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)=[O:6])[CH2:62]1)([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53]

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 213410713-(r)-t-Butyldimethylsilyloxymethyl-4-(s)-(3-fluorophenyl)pyrrolidineHCID 572601153-Ethyl-2-hydroxyvaleric acid, 4-methoxybenzyl ester

Product 1

HCID 573143532-(3-(R)-t-Butydimethylsilyloxymethyl-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)-3-ethylvaleric Acid, 4-methoxybenzyl EsterYield 67.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 0.82 g (2.93 mmol) of 3-Ethyl-2-hydroxyvaleric acid, 4-methoxybenzyl ester (step B) in 5 mL of dry CH2Cl2 was cooled in a −78° C. bath and 0.6 mL (3.57 mmol) of trifluoromethanesulfonic anhydride was added. After 5 min, 0.46 mL (4 mmol) of 2,6-lutidine was added and stirred for 15 min. To this solution, 1.3 mL (7.47 mmol) of DIEA was added and after 10 min a solution of 0.907 g (2.93 mmol) of 3-(R)-t-butyldimethylsilyloxymethyl-4-(S)-(3-fluorophenyl)pyrrolidine in 5 mL of CH2Cl2 was added. The cold bath was removed and the reaction was stirred overnight. The reaction was quenched with saturated NaHCO3 and extracted with Et2O. The combined Et2O layer was washed with brine, dried and concentrated. The residue was purified on a flash column using 10% EtOAc-hexane to isolate 1.1 g of the desired product as a mixture of two diastereomers. 1H NMR (CDCl3) 0.06 and 0.16 (6H), 0.87 (m, 15H), 1.2-3.6 (m, 13H), 3.82 (2s, 3H), 5.11 (s, 2H), 6.8-7.4 (m, 8H),

Workup

  1. additionwas added
  2. customThe cold bath was removed
  3. stirringthe reaction was stirred overnight
  4. customThe reaction was quenched with saturated NaHCO3
  5. extractionextracted with Et2O
  6. washThe combined Et2O layer was washed with brine
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified on a flash column

Sources & evidence

ORD record
ord-b73067f6f33b456f9b3d6f5216b66397
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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