Hydrazine hydrate (1:1) → tert-Butyl 4-(6-amino-7-fluoro-2H-benzo[b][1,4]thiazin-4(3H)-yl)piperidine-1-carboxylate

HRID 1917249Notes

Reaction equation

HRID 1917249 reaction equation
[F:1][C:2]1[C:3]([N+:25]([O-])=O)=[CH:4][C:5]2[N:10]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[CH2:9][CH2:8][S:7][C:6]=2[CH:24]=1.O.NN>O1CCCC1.CO.C(OCC)(=O)C.[Ni]>[NH2:25][C:3]1[C:2]([F:1])=[CH:24][C:6]2[S:7][CH2:8][CH2:9][N:10]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[C:5]=2[CH:4]=1

Participants

7

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 59144166tert-Butyl 4-(7-fluoro-6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)piperidine-1-carboxylate

Product 1

HCID 59144114tert-Butyl 4-(6-amino-7-fluoro-2H-benzo[b][1,4]thiazin-4(3H)-yl)piperidine-1-carboxylateYield 98%

Reagents, catalysts & solvents 4

HCID 935NickelCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of tert-butyl 4-(7-fluoro-6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)piperidine-1-carboxylate (190 mg, 0.478 mmol) in tetrahydrofuran (3.00 mL) was added Raney-Nickel (28.1 mg, 0.478 mmol) as a suspension in methanol (3 mL). To this mixture was then added hydrazine hydrate (0.233 mL, 4.78 mmol), and the resulting mixture was stirred at 60° C. for 8 minutes. During this time, the reaction mixture turns light red. The mixture was then diluted with ethyl acetate and washed with saturated sodium carbonate (2×), water (2×), and brine. The organic phase was dried, filtered, and concentrated, giving a red oil (172 mg, 98%). 1H NMR (DMSO-d6) δ 6.61 (d, J=11.1 Hz, 1H), 6.34 (d, J=8.4 Hz, 1H), 4.76 (s, 2H), 4.11-4.01 (m, 2H), 3.62-3.51 (m, 1H), 3.29-3.25 (m, 2H), 2.93-2.88 (m, 2H), 2.87-2.69 (m, 2H), 1.71-1.61 (m, 2H), 1.59-1.48 (m, 2H), 1.40 (m, 9H); ESI-MS (m/z, %): 368 (MH+, 25), 312 (100).

Workup

  1. washwashed with saturated sodium carbonate (2×), water (2×), and brine
  2. customThe organic phase was dried
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-e7d02f93988843e18b0ce9eeee30d2e3
Source dataset
uspto-grants-2013_12
Patent number
US08618286B2

Reaction notes

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