Pyrrolidine → N-((1S,2R,3R,4R,6R)-2,3-bis(benzyloxy)-4-((benzyloxy)methyl)-6-hydroxycyclohexyl)pyrrolidine-1-carbothioamide

HRID 2274309Notes

Reaction equation

HRID 2274309 reaction equation
[NH2:1][C@@H:2]1[C@@H:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C@H:6]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:5]([CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:4][C@H:3]1[OH:33].C1N=CN([C:39]([N:41]2[CH:45]=N[CH:43]=[CH:42]2)=[S:40])C=1.N1CCC[CH2:47]1>C(Cl)Cl>[CH2:9]([O:8][C@H:7]1[C@H:6]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C@@H:5]([CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:4][C@@H:3]([OH:33])[C@@H:2]1[NH:1][C:39]([N:41]1[CH2:42][CH2:43][CH2:47][CH2:45]1)=[S:40])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 802641,1'-ThiocarbonyldiimidazoleHCID 86727203(1R,2S,3R,4R,5R)-2-Amino-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)cyclohexanol

Product 1

HCID 86727204N-((1S,2R,3R,4R,6R)-2,3-bis(benzyloxy)-4-((benzyloxy)methyl)-6-hydroxycyclohexyl)pyrrolidine-1-carbothioamideYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (1R,2S,3R,4R,5R)-2-amino-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)cyclohexanol (0.210 g, 0.469 mmol), 1,1-thiocarbonyldiimidazole (Thio-CDI) (0.125 g, 0.704 mmol) in DCM (10 mL) was stirred at room temperature for 3 h. Pyrrolidine (0.10 mL) was then added, and the mixture was further stirred for 1 h. The solvent was removed under reduced pressure, and the residue was purified on silica gel by automatic flash column chromatography (EtOAc/hexanes, 2:3 to 4:1), affording the product as a pale yellow solid (0.26 g, 99%). 1H NMR (400 MHz, CDCl3) δ 7.29-7.16 (m, 15H), 5.06 (d, J=7.5 Hz, 1H), 4.77 (d, J=12.0 Hz, 1H), 4.71 (d, J=10.8 Hz, 1H), 4.70-4.66 (m, 1H), 4.57 (d, J=12.0 Hz, 1H), 4.50 (d, J=10.8 Hz, 1H), 4.42 (s, 2H), 4.19 (s, broad, 1H), 3.65 (t, J=8.8 Hz, 1H), 3.56 (dd, J=4.5, 8.8 Hz, 1H), 3.51-3.40 (m, 3H), 2.07-2.02 (m, 1H), 1.76-1.62 (m, 6H).

Workup

  1. stirringthe mixture was further stirred for 1 h
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was purified on silica gel by automatic flash column chromatography (EtOAc/hexanes, 2:3 to 4:1)

Sources & evidence

ORD record
ord-dc4f61801986481bb5a7c5251c5ce092
Source dataset
uspto-grants-2015_09
Patent number
US09126957B2

Reaction notes

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