Trifluoromethanesulfonic anhydride → (R)-3-methoxy-1-((S)-1-(trityloxy)propan-2-yl)pyrrolidine

HRID 714596Notes

Reaction equation

HRID 714596 reaction equation
S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[C:16]([O:35][CH2:36][C@H:37](O)[CH3:38])([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(C(C)C)CC)(C)C.Cl.[CH3:50][O:51][C@@H:52]1[CH2:56][CH2:55][NH:54][CH2:53]1>C(Cl)Cl>[CH3:50][O:51][C@@H:52]1[CH2:56][CH2:55][N:54]([C@@H:37]([CH3:38])[CH2:36][O:35][C:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:53]1

Participants

6

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531Diisopropylethylamine2×HCID 11067110(2R)-1-(triphenylmethoxy)-2-propanolHCID 45789898(3R)-3-methoxypyrrolidine hydrochloride

Product 1

HCID 89619838(R)-3-methoxy-1-((S)-1-(trityloxy)propan-2-yl)pyrrolidineYield 65.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

Triflic anhydride (1M in DCM, 1.67 mL, 1.67 mmol) was added to a solution of (R)-1-(trityloxy)propan-2-ol (505 mg, 1.59 mmol) and diisopropylethylamine (0.55 mL, 3.16 mmol) in DCM (10 mL) at −78° C. The reaction was allowed to warm to −20° C. over 1 h. Diisopropylethylamine (0.32 mL, 1.84 mmol) and (R)-3-methoxypyrrolidine hydrochloride (255 mg, 1.85 mmol) were added to the reaction and the mixture was allowed to warm to room temperature over 3 h. The reaction mixture was washed with 2×10 mL saturated aqueous NaHCO3, washed with 10 mL brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography to yield (R)-3-methoxy-1-((S)-1-(trityloxy)propan-2-yl)pyrrolidine (420 mg). 1H NMR (DMSO-d6): δ 7.40-7.20 (m, 15H), 3.76 (m, 1H), 3.26 (m, 1H), 3.11 (s, 3H), 3.09 (m, 1H), 2.82 (m, 1H), 2.64 (m, 1H), 2.48 (m, 1H), 2.38 (m, 2H), 1.84 (m, 1H), 1.55 (m, 1H), 1.05 (d, 3H).

Workup

  1. temperatureto warm to room temperature over 3 h
  2. washThe reaction mixture was washed with 2×10 mL saturated aqueous NaHCO3
  3. washwashed with 10 mL brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-a0efa3c3c3cf46ccb61840f9b6eab684
Source dataset
uspto-grants-2015_11
Patent number
US09187460B2

Reaction notes

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