Diisopropylethylamine → (R)-N-[(3S,6R)-6-(tert-butyl-dimethyl-silanyloxy)2-oxo-1-pyridin-3-ylmethyl-azepan-3-yl]-2-[(4R,5R,6R)-6-((E)-3,3-dimethyl-but-1-enyl)-5-hydroxy-2,2-dimethyl-[1,3]dioxan-4-yl]-2-methoxy-acetamide

HRID 2224021Notes

Reaction equation

HRID 2224021 reaction equation
[NH2:1][C@H:2]1[CH2:8][CH2:7][C@@H:6]([O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])[CH2:5][N:4]([CH2:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[C:3]1=[O:24].[CH3:25][C:26]([CH3:44])([CH3:43])/[CH:27]=[CH:28]/[C@H:29]1[O:34][C:33]([CH3:36])([CH3:35])[O:32][CH:31]2[CH:37]([O:41][CH3:42])[C:38](=[O:40])[O:39][C@H:30]12.C(N(C(C)C)CC)(C)C>C(O)(C)C>[C:13]([Si:10]([CH3:12])([CH3:11])[O:9][C@H:6]1[CH2:5][N:4]([CH2:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[C:3](=[O:24])[C@@H:2]([NH:1][C:38](=[O:40])[C@@H:37]([C@H:31]2[C@H:30]([OH:39])[C@@H:29](/[CH:28]=[CH:27]/[C:26]([CH3:43])([CH3:25])[CH3:44])[O:34][C:33]([CH3:36])([CH3:35])[O:32]2)[O:41][CH3:42])[CH2:8][CH2:7]1)([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 69267176(3S,6R)-3-amino-6-(tert-butyl-dimethyl-silanyloxy)-1-pyridin-3-ylmethyl-azepan-2-oneHCID 69267460(4R,4aR)-((E)-3,3-dimethyl-but-1-enyl)-7-methoxy-2,2-dimethyl-tetrahydro-furo[3,2-d][1,3]dioxin-6-one

Product 1

HCID 69266828(R)-N-[(3S,6R)-6-(tert-butyl-dimethyl-silanyloxy)2-oxo-1-pyridin-3-ylmethyl-azepan-3-yl]-2-[(4R,5R,6R)-6-((E)-3,3-dimethyl-but-1-enyl)-5-hydroxy-2,2-dimethyl-[1,3]dioxan-4-yl]-2-methoxy-acetamideYield 57.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of (3S,6R)-3-amino-6-(tert-butyl-dimethyl-silanyloxy)-1-pyridin-3-ylmethyl-azepan-2-one (1.84 g, 5.3 mmol), (4R,4aR)-4-((E)-3,3-Dimethyl-but-1-enyl)-7-methoxy-2,2-dimethyl-tetrahydro-furo[3,2-d][1,3]dioxin-6-one (1.0 g, 3.5 mmol) and diisopropylethylamine (1.37 g, 11.0 mmol) in isopropanol (10 mL) is refluxed for 16 h. The solution is evaporated and chromatographed on silica (95% CH2Cl2/5% CH3OH) to give 1.27 g (57.0%) of (R)-N-[(3S,6R)-6-(tert-butyl-dimethyl-silanyloxy)2-oxo-1-pyridin-3-ylmethyl-azepan-3-yl]-2-[(4R,5R,6R)-6-((E)-3,3-dimethyl-but-1-enyl)-5-hydroxy-2,2-dimethyl-[1,3]dioxan-4-yl]-2-methoxy-acetamide as a white solid. MS (ESI) 634.3 (M+H)+

Workup

  1. customThe solution is evaporated
  2. customchromatographed on silica (95% CH2Cl2/5% CH3OH)

Sources & evidence

ORD record
ord-af1aedd5e5bc42d096a4f7df4129dc1f
Source dataset
uspto-grants-2008_05
Patent number
US07378410B2

Reaction notes

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