2-Methyl-6-nitrobenzoic anhydride → tert-butyl (3S,7S,8R,9S)-7-benzyl-9-methyl-2-oxo-8-(triisopropylsilyloxy)-1,5-dioxonan-3-ylcarbamate

HRID 75735Notes

Reaction equation

HRID 75735 reaction equation
CC1C=CC=C([N+]([O-])=O)C=1C(OC(=O)C1C([N+]([O-])=O)=CC=CC=1C)=O.[CH2:26]([C@H:33]([C@@H:49]([O:53][Si:54]([CH:61]([CH3:63])[CH3:62])([CH:58]([CH3:60])[CH3:59])[CH:55]([CH3:57])[CH3:56])[C@@H:50]([OH:52])[CH3:51])[CH2:34][O:35][CH2:36][C@@H:37]([NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C:38](O)=[O:39])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:26]([C@@H:33]1[C@@H:49]([O:53][Si:54]([CH:61]([CH3:63])[CH3:62])([CH:58]([CH3:60])[CH3:59])[CH:55]([CH3:56])[CH3:57])[C@H:50]([CH3:51])[O:52][C:38](=[O:39])[C@@H:37]([NH:41][C:42](=[O:43])[O:44][C:45]([CH3:47])([CH3:48])[CH3:46])[CH2:36][O:35][CH2:34]1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

5

Reactant 2

HCID 104726482-Methyl-6-nitrobenzoic anhydrideHCID 86701224(R)-3-((2S,3R,4S)-2-benzyl-4-hydroxy-3-(triisopropylsilyloxy)pentyloxy)-2-(tert-butoxycarbonylamino)propanoic acid

Product 1

HCID 86701226tert-butyl (3S,7S,8R,9S)-7-benzyl-9-methyl-2-oxo-8-(triisopropylsilyloxy)-1,5-dioxonan-3-ylcarbamateYield 98.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of DMAP (442 mg, 3.62 mmol, 6.00 equiv) and 2-methyl-6-nitrobenzoic anhydride (415 mg, 1.21 mmol, 2.00 equiv) in CH2Cl2 (92 mL, 6.5 mM) was added a solution of (R)-3-((2S,3R,4S)-2-benzyl-4-hydroxy-3-(triisopropylsilyloxy)pentyloxy)-2-(tert-butoxycarbonylamino)propanoic acid (334 mg, 0.603 mmol, 1.00 equiv) in CH2Cl2 (15 mL) via a syringe pump over 8 h. The resulting solution was stirred at room temperature for an additional 8 h, concentrated, and purified by automated silica gel column chromatography (0-20% hexanes in acetone) to provide tert-butyl (3S,7S,8R,9S)-7-benzyl-9-methyl-2-oxo-8-(triisopropylsilyloxy)-1,5-dioxonan-3-ylcarbamate (318 mg, 98%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.34-7.07 (m, 5H), 5.30-5.14 (m, 1H), 5.11 (d, J=8.1 Hz, 1H), 4.53 (q, J=8.3 Hz, 1H), 4.08 (dd, J=11.6, 6.9 Hz, 1H), 3.88 (dd, J=6.3, 5.0 Hz, 1H), 3.60 (dd, J=11.7, 5.9 Hz, 1H), 3.44 (d, J=11.6 Hz, 1H), 3.07 (t, J=10.3 Hz, 1H), 2.92 (dd, J=13.3, 4.0 Hz, 1H), 2.76 (t, J=12.4 Hz, 1H), 1.99 (td, J=10.6, 5.0 Hz, 1H), 1.50-1.38 (m, 12H), 1.14-0.99 (m, 21H); 13C NMR (101 MHz, CDCl3) δ 171.75, 154.92, 140.37, 129.13, 128.35, 126.01, 79.99, 78.88, 73.17, 70.69, 52.89, 49.64, 34.63, 28.28, 19.51, 18.24, 18.19, 13.14; HRMS-ESI (m/z) [M+H]+ calc'd for C29H49NO6SiNa, 558.3221. found, 558.3224.

Workup

  1. concentrationconcentrated
  2. custompurified by automated silica gel column chromatography (0-20% hexanes in acetone)

Sources & evidence

ORD record
ord-a4d5aca7fc054a41b8fce7b893c8ef95
Source dataset
uspto-grants-2014_09
Patent number
US08835462B2

Reaction notes

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