Allyl bromide → tert-butyl ((5R,6R)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate

HRID 627601Notes

Reaction equation

HRID 627601 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[C@:11]1([CH3:29])[CH2:16][S:15](=[O:18])(=[O:17])[C:14]([CH3:20])([CH3:19])[C:13]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[N:12]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:40](Br)[CH:41]=[CH2:42]>C1COCC1>[CH2:42]([C@H:16]1[S:15](=[O:18])(=[O:17])[C:14]([CH3:20])([CH3:19])[C:13]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[N:12][C@@:11]1([C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[F:1])[CH3:29])[CH:41]=[CH2:40].[CH2:42]([C@@H:16]1[S:15](=[O:18])(=[O:17])[C:14]([CH3:20])([CH3:19])[C:13]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[N:12][C@@:11]1([C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[F:1])[CH3:29])[CH:41]=[CH2:40]

Participants

6

Reactant 3

HCID 7841Allyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 86728098(R)-tert-butyl (5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate

Product 2

HCID 86728097tert-butyl ((5R,6R)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamateYield 25.9%HCID 86728122tert-butyl ((5R,6S)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (R)-tert-butyl (5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (600 mg, 1.397 mmol) in THF (14 ml) was added potassium bis(trimethylsilyl)amide, (1M in THF) (8.38 ml, 8.38 mmol) dropwise at −78° C. and the mixture was stirred for 30 min at −78° C. Neat allyl bromide (0.363 ml, 4.19 mmol) was then added dropwise and the mixture was stirred for 30 min. The reaction mixture was quenched with sat. aq. NH4Cl solution at −78° C., then allowed to reach RT and extracted with ethyl acetate. The organic extracts were washed with brine and concentrated. The residue was separated by silica gel chromatography on a 40 g RediSep Gold column using 10-60% EtOAc/heptane solvent gradient to afford less polar trans-isomer tert-butyl ((5R,6R)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (170 mg, 0.362 mmol, 25.9% yield), and more polar cis-isomer tert-butyl ((5R,6S)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (263 mg, 0.560 mmol).

Workup

  1. stirringthe mixture was stirred for 30 min
  2. customThe reaction mixture was quenched with sat. aq. NH4Cl solution at −78° C.
  3. customto reach RT
  4. extractionextracted with ethyl acetate
  5. washThe organic extracts were washed with brine
  6. concentrationconcentrated
  7. customThe residue was separated by silica gel chromatography on a 40 g RediSep Gold column

Sources & evidence

ORD record
ord-da5c03707e284c7ca30a3ad915964505
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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