Sodium Azide → HCID 89573786, compound

HRID 1911007Notes

Reaction equation

HRID 1911007 reaction equation
Br[C:2]1[CH:23]=[C:22]2[C:5]([CH2:6][CH2:7][C@@H:8]3[CH2:13][S:12][C:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[N:10][C@@:9]32[CH3:24])=[CH:4][CH:3]=1.[N-:25]=[N+:26]=[N-:27].[Na+].CN[C@@H]1CCCC[C@H]1NC.[Na].O=C1O[C@H]([C@H](CO)O)C(O)=C1O>C(O)C.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].O>[N:25]([C:2]1[CH:23]=[C:22]2[C:5]([CH2:6][CH2:7][C@@H:8]3[CH2:13][S:12][C:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[N:10][C@@:9]32[CH3:24])=[CH:4][CH:3]=1)=[N+:26]=[N-:27]

Participants

8

Reactant 4

HCID 33557Sodium AzideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 66586226sodium L-ascorbic acidHCID 71084845HCID 71084845, compound

Product 1

HCID 89573786HCID 89573786, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 24463Copper sulfate pentahydrateCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl rel-((4aS,10bS)-9-bromo-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate from preparation C (300 mg, 0.729 mmol) in ethanol (3.6 mL) was added sodium azide (228 mg, 3.51 mmol), trans-1,2-bis(methylamino)cyclohexane (55 mg, 0.387 mmol), 0.66 M solution of aqueous L-ascorbic acid sodium salt (0.780 mL, 0.515 mmol) and water (0.70 mL) and the mixture was purged with nitrogen for 10 min. A 0.33 M solution of aqueous copper(II) sulfate pentahydrate (0.780 mL, 0.257 mmol) was added and the reaction was heated to 80° C. for 12 min. The reaction was poured into water and was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified using silica gel column chromatography (2:1 hexanes/EtOAc) to afford tert-butyl rel-((4aS,10bS)-9-azido-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate (190 mg, 0.509 mmol, 70% yield) as a clear viscous oil. LCMS (M+Na)+=396.1. 1H NMR (500 MHz, chloroform-d) δ 7.11 (br. s., 1H), 7.09 (d, J=8.2 Hz, 1H), 6.89 (dd, J=8.2, 2.1 Hz, 1H), 3.03 (dd, J=12.9, 3.6 Hz, 1H), 2.94-2.79 (m, 3H), 2.27 (br. s., 1H), 2.21-2.07 (m, 1H), 1.99 (dq, J=13.8, 6.7 Hz, 1H), 1.62 (s, 3H), 1.48 (s, 9H).

Workup

  1. customthe mixture was purged with nitrogen for 10 min
  2. extractionwas extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified

Sources & evidence

ORD record
ord-7fc9b8dba87045a281373d20499f30bf
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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