Ethyl Acetate → HCID 117629119, compound

HRID 61969Notes

Reaction equation

HRID 61969 reaction equation
[N:1]([CH2:4][C@@H:5]([CH3:32])[C:6]([O:8][C@H:9]1[C@H:14]([CH3:15])[O:13][C@@H:12]([O:16][C@H:17]([CH3:30])[CH2:18][CH2:19][C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[C@H:11]([OH:31])[CH2:10]1)=[O:7])=[N+:2]=[N-:3].[CH2:33]([O:40][C@@H:41]1[CH2:46][C@@H:45]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C@H:44]([CH3:55])[O:43][C@H:42]1[O:56][CH2:57][CH2:58][CH2:59][CH2:60][C:61](O)=[O:62])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CCN=C=NCCCN(C)C.Cl.C(OCC)(=O)C>ClCCl.CN(C)C1C=CN=CC=1.CCCCCC>[CH2:33]([O:40][C@@H:41]1[CH2:46][C@@H:45]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C@H:44]([CH3:55])[O:43][C@H:42]1[O:56][CH2:57][CH2:58][CH2:59][CH2:60][C:61]([O:31][C@@H:11]1[CH2:10][C@@H:9]([O:8][C:6](=[O:7])[C@H:5]([CH3:32])[CH2:4][N:1]=[N+:2]=[N-:3])[C@H:14]([CH3:15])[O:13][C@H:12]1[O:16][C@@H:17]([CH2:18][CH2:19][C:20]([O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21])[CH3:30])=[O:62])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 712548705-(((2R,3R,5R,6S)-3,5-bis(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)pentanoic acidHCID 131737184HCID 131737184, compound

Product 1

HCID 117629119HCID 117629119, compoundYield 97%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

To prepare 40, a solution of 8 (5.2 mg, 11.6 μmol) and 10 (6.4 mg, 14.9 μmol) in 1 mL dichloromethane was treated with 4-dimethylaminopyridine (3.7 mg, 30 μmol) and EDC hydrochloride (5.8 mg, 30 μmol). After stirring at room temperature for 12 hours the reaction was quenched by addition of 5% aqueous acetic acid (50 μl), dried over Na2SO4, and concentrated in vacuo. Flash column chromatography on silica using a gradient of 0-50% ethyl acetate in hexane afforded (2R,3R,5R,6S)-5-(((R)-3-azido-2-methylpropanoyl)oxy)-2-(((R)-5-(benzyloxy)-5-oxopentan-2-yl)oxy)-6-methyltetrahydro-2H-pyran-3-yl 5-(((2R,3R,5R,6S)-3,5-bis(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)pentanoate (40) (9.6 mg, 11.2 μmol, 97%) as a colorless oil. 1H NMR (500 MHz, acetone-d6): δ (ppm) 7.40-7.25 (m, 15H), 5.15 (d, J=12.3 Hz, 1H), 5.12 (d, J=12.3 Hz, 1H), 4.84-4.78 (m, 2H), 4.66 (s, 1H), 4.74 (s, 1H), 4.58 (d, J=12.3 Hz, 1H), 4.57 (d, J=11.4 Hz, 1H), 4.53 (d, J=12.3 Hz, 1H), 4.46 (d, J=11.4 Hz, 1H), 3.87-3.80 (m, 2H), 3.75-3.67 (m, 2H), 3.60-3.56 (m, 1H), 3.51 (dd, J=12.2 Hz, 7.6 Hz, 1H), 3.47-3.34 (m, 3H), 2.68-2.60 (m, 1H), 2.55-2.41 (m, 2H), 2.38 (t, J=7.4 Hz, 2H), 2.24-2.18 (m, 1H), 2.12-2.06 (m, 1H), 1.96-1.85 (m, 3H), 1.77-1.65 (m, 3H), 1.64-1.55 (m, 2H), 1.29 (d, J=6.2 Hz, 3H), 1.19 (d, J=7.1 Hz, 3H), 1.16 (d, J=6.2 Hz, 3H), 1.15 (d, J=6.1 Hz, 3H). 13C NMR (125 MHz, acetone-d6): δ (ppm) 173.4, 173.2, 172.9, 138.6, 138.5, 136.0, 128.7, 128.52, 128.51, 128.45, 128.38, 128.0, 127.79, 127.77, 97.2, 93.5, 75.6, 75.4, 71.4, 71.24, 71.22, 70.5, 70.4, 68.3, 67.0, 66.8, 66.5, 55.8, 40.1, 34.1, 32.1, 30.6, 29.9, 29.7, 29.5, 29.1, 21.8, 18.9, 18.3, 17.7, 14.9. ESI+ MS: m/z=882.5 [M+Na+] and 898.5 [M+K+]. See FIGS. 107A-B.

Workup

  1. customTo prepare 40
  2. customwas quenched by addition of 5% aqueous acetic acid (50 μl)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0b85882116704415b14de546bbe31ed7
Source dataset
uspto-grants-2016_09
Patent number
US09445596B2

Reaction notes

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