(S)-(+)-2-(Methoxymethyl)pyrrolidine → (S)-2-Methoxymethyl-1-{4-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]tetrahydropyran-4-ylmethyl}pyrrolidine

HRID 272871Notes

Reaction equation

HRID 272871 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH:22]=O)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:24][O:25][CH2:26][C@@H:27]1[CH2:31][CH2:30][CH2:29][NH:28]1>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[CH3:24][O:25][CH2:26][C@@H:27]1[CH2:31][CH2:30][CH2:29][N:28]1[CH2:22][C:16]1([C:13]2[CH:12]=[CH:11][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:15][CH:14]=2)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1

Participants

5

Reactant 2

HCID 671217(S)-(+)-2-(Methoxymethyl)pyrrolidineHCID 598374274-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde

Product 1

HCID 11553469(S)-2-Methoxymethyl-1-{4-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]tetrahydropyran-4-ylmethyl}pyrrolidineYield 72%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde (350 mg, 1.103 mmol), (s)-(+)-2-(methoxymethyl)pyrrolidine (230 mg, 2.00 mmol), absolute ethanol (40 ml), activated 3 Å molecular sieves (350 mg), titanium (IV) isopropoxide (1.62 ml, 5.48 mmol) and STAB (2.09, 9.74 mmol) were reacted in accordance with the general procedure D. The isolated crude product was purified by column chromatography on silica eluting with DCM:MeOH:NH3 (98:1:1) to give the title compound as a white solid (330 mg, 72%). 1H NMR (400 MHz, CDCl3) δ7.18 (d, 2H), 6.86 (d, 2H), 4.02 (t, 2H), 3.84-3.70 (m, 2H), 3.59 (td, 1H), 3.45 (td, 1H), 3.27 (s, 3H), 3.10 (dd, 1H), 3.02 (dd, 1H), 2.94 (d, 1H), 2.63 (t, 2H), 2.59-2.45 (m, 5H), 2.39 (m, 1H), 2.21 (m, 1H), 2.06-1.34 (m, 15H).

Workup

  1. customThe isolated crude product
  2. customwas purified by column chromatography on silica eluting with DCM:MeOH:NH3 (98:1:1)

Sources & evidence

ORD record
ord-44d7b876450142258daf4d8c12250f03
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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