Methyl morpholine oxide → tert-butyl (1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-4-methylpentylcarbamate

HRID 660397Notes

Reaction equation

HRID 660397 reaction equation
C[N+]1([O-])CCOCC1.[OH:9][C@@H:10]([CH2:40][C@H:41]([CH2:45][OH:46])[CH:42]([CH3:44])[CH3:43])[C@@H:11]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH2:12][C@H:13]([CH2:17][C:18]1[CH:26]=[C:25]2[C:21]([CH:22]=[N:23][N:24]2[CH2:27][CH2:28][CH2:29][O:30][CH3:31])=[CH:20][CH:19]=1)[CH:14]([CH3:16])[CH3:15]>C(Cl)Cl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[CH:42]([C@H:41]1[C:45](=[O:46])[O:9][C@H:10]([C@@H:11]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:36])([CH3:37])[CH3:38])[CH2:12][C@H:13]([CH2:17][C:18]2[CH:26]=[C:25]3[C:21]([CH:22]=[N:23][N:24]3[CH2:27][CH2:28][CH2:29][O:30][CH3:31])=[CH:20][CH:19]=2)[CH:14]([CH3:15])[CH3:16])[CH2:40]1)([CH3:44])[CH3:43]

Participants

5

Reactant 2

HCID 82029Methyl morpholine oxideHCID 59630975tert-butyl (3S,5S,6S,8S)-6-hydroxy-8-(hydroxymethyl)-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-2,9-dimethyldecan-5-ylcarbamate

Product 1

HCID 59630995tert-butyl (1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-4-methylpentylcarbamateYield 37%

Reagents, catalysts & solvents 2

HCID 178419074HCID 178419074, compoundCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of N-methylmorpholine-N-oxide (270 mg, 2 mmol) in dry CH2Cl2 (10 mL) was added activated 4 Å molecular sieves (500 mg) at rt under N2. After stirring for 2 h this mixture was added to a mixture of tetrapropylammonium perruthenate (22 mg, 0.062 mmol) and tert-butyl (3S,5S,6S,8S)-6-hydroxy-8-(hydroxymethyl)-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-2,9-dimethyldecan-5-ylcarbamate (0.33 g, 0.62 mmol) in dry CH2Cl2 (20 mL). The mixture was stirred overnight and filtered through a pad of silica gel. The filtrate was washed with water and brine, evaporated, and purified by flash chromatography on silica gel to afford tert-butyl (1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-4-methylpentylcarbamate (120 mg, 37%). 1H NMR (400 MHz, CDCl3): δ7.93 (s, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.20 (s, 1H), 6.98 (d, J=8.0 Hz, 1H), 4.46-4.38 (m, 4H), 3.89 (m, 1H), 3.29 (s, 6H), 2.86 (m, 1H), 2.58-2.52 (m, 2H), 2.18-2.2.08 (m, 5H), 1.70 (m, 2H), 1.47 (s, 9H), 1.04 (d, J=6.4 Hz, 3H), 1.00 (d, J=6.8 Hz, 3H), 0.92 (d, J=6.4 Hz, 3H), 0.89 (d, J=6.4 Hz, 3H); MS: 530 (M++1)

Workup

  1. customat rt
  2. stirringThe mixture was stirred overnight
  3. filtrationfiltered through a pad of silica gel
  4. washThe filtrate was washed with water and brine
  5. customevaporated
  6. custompurified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-3ca78846f236476882f33b42147e004c
Source dataset
uspto-grants-2011_12
Patent number
US08084485B2

Reaction notes

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