Toluene → (R)-3-((R)-2-amino-3-(1-(hydroxymethyl)cyclopropylamino)-3-oxopropylthio)propane-1,2-diyl didodecanoate

HRID 2204944Notes

Reaction equation

HRID 2204944 reaction equation
[C:1]([O:14][CH2:15][C@@H:16]([O:47][C:48](=[O:60])[CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH3:59])[CH2:17][S:18][CH2:19][C@H:20]([NH:29]C(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O)[C:21]([NH:23][C:24]1([CH2:27][OH:28])[CH2:26][CH2:25]1)=[O:22])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].N1CCCCC1.C1(C)C=CC=CC=1>C(#N)C.C(Cl)Cl>[C:1]([O:14][CH2:15][C@@H:16]([O:47][C:48](=[O:60])[CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH3:59])[CH2:17][S:18][CH2:19][C@H:20]([NH2:29])[C:21]([NH:23][C:24]1([CH2:27][OH:28])[CH2:25][CH2:26]1)=[O:22])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]

Participants

6

Reactant 3

HCID 1140TolueneHCID 8082PiperidineHCID 67414699(R)-3-((R)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(1-(hydroxymethyl)-cyclopropylamino)-3-oxopropylthio)propane-1,2-diyl didodecanoate

Product 1

HCID 53475990(R)-3-((R)-2-amino-3-(1-(hydroxymethyl)cyclopropylamino)-3-oxopropylthio)propane-1,2-diyl didodecanoate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-3-((R)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(1-(hydroxymethyl)-cyclopropylamino)-3-oxopropylthio)propane-1,2-diyl didodecanoate (1 eq) was added 20% piperidine (50 eq) in acetonitrile. The resulting gel was diluted with DCM and sonicated for 3 minutes. The mixture was added to toluene and then concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 100% EtOAc then 0-10% MeOH/DCM to give (R)-3-((R)-2-amino-3-(1-(hydroxymethyl)cyclopropylamino)-3-oxopropylthio)propane-1,2-diyl didodecanoate as an off white solid. 1H NMR (CDCl3): δ 7.85 (br s, 1H), 5.11-5.18 (m, 1H), 4.36 (dd, 1H), 4.14 (dd, 1H), 4.05 (br s, 1H), 3.59 (q, 2H), 3.50 (dd, 1H), 3.06 (dd, 1H), 2.80 (dd, 1H), 2.68-2.76 (m, 2H), 2.32 (q, 4H), 1.51-1.68 (m, 4H), 1.19-1.35 (m, 32H), 0.90-0.94 (m, 2H), 0.88 (t, 6H), 0.79-0.83 (m, 2H). LRMS [M+H]=629.5.

Workup

  1. customsonicated for 3 minutes
  2. concentrationconcentrated en vaccuo
  3. customThe crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-0224cfd076e14fa5b0c21865f96a16da
Source dataset
uspto-grants-2016_06
Patent number
US09365506B2

Reaction notes

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