Isopropanol → HCID 131737184, compound

HRID 61968Notes

Reaction equation

HRID 61968 reaction equation
[OH:1][C@@H:2]1[CH2:7][C@@H:6]([OH:8])[C@H:5]([CH3:9])[O:4][C@H:3]1[O:10][C@H:11]([CH3:24])[CH2:12][CH2:13][C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15].[N:25]([CH2:28][C@@H:29]([CH3:33])[C:30](O)=[O:31])=[N+:26]=[N-:27].CCN=C=NCCCN(C)C.Cl.C(O)(C)C>ClCCl.CN(C)C1C=CN=CC=1>[N:25]([CH2:28][C@@H:29]([CH3:33])[C:30]([O:8][C@H:6]1[C@H:5]([CH3:9])[O:4][C@@H:3]([O:10][C@H:11]([CH3:24])[CH2:12][CH2:13][C:14]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])[C@H:2]([OH:1])[CH2:7]1)=[O:31])=[N+:26]=[N-:27]

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 13116883HCID 13116883, compoundHCID 131737185HCID 131737185, compound

Product 1

HCID 131737184HCID 131737184, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To prepare 8, a solution of 38 (22.6 mg, 66.8 μmol) and 3-azido-(2R)-methylpropanoic acid (Rej et al., J. Org. Chem. 61:6289-95 (1996), which is hereby incorporated by reference in its entirety) (37, 8.6 mg, 66.8 μmol) in 2 mL dichloromethane was treated with 4-dimethylaminopyridine (16.3 mg, 133.6 μmol) and EDC hydrochloride (25.7 mg, 133.6 μmol). After stirring at room temperature for 12 hours the reaction was quenched by addition of 5% aqueous acetic acid (100 μl), dried over Na2SO4, and concentrated in vacuo. Flash column chromatography on silica using a gradient of 0-10% isopropanol in dichloromethane afforded (R)-benzyl 4-(((2R,3R,5R,6S)-5-(((R)-3-azido-2-methylpropanoyl)oxy)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)pentanoate (8) (5.2 mg, 11.6 μmol, 17%) as a colorless oil. 1H NMR (400 MHz, chloroform-d): δ (ppm) 7.40-7.31 (m, 5H), 5.15 (d, J=13.6 Hz, 1H), 5.11 (d, J=13.6 Hz, 1H), 4.86 (ddd, J=10.9 Hz, 9.4 Hz, 4.6 Hz, 1H), 4.73-4.70 (m, 1H), 3.90-3.76 (m, 3H), 3.52 (dd, J=12.2 Hz, 7.5 Hz, 1H), 3.38 (dd, J=12.2 Hz, 5.6 Hz, 1H), 2.71-2.60 (m, 1H), 2.57-2.42 (m, 2H), 2.13-2.05 (m, 2H), 1.93-1.83 (m, 3H), 1.20 (d, J=7.0 Hz, 3H), 1.17 (d, J=6.3 Hz, 3H), 1.16 (d, J=6.2 Hz, 3H). See FIG. 105.

Workup

  1. customTo prepare 8
  2. customwas quenched by addition of 5% aqueous acetic acid (100 μl)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-13cec8968eb84c5dbaa663c4289cd233
Source dataset
uspto-grants-2016_09
Patent number
US09445596B2

Reaction notes

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