1,2-Diaminocyclohexane → HCID 57504888, compound

HRID 2060756Notes

Reaction equation

HRID 2060756 reaction equation
[Na].[O:2]=[C:3]1[O:9][C@H:8]([C@H:10]([CH2:12][OH:13])[OH:11])[C:6]([OH:7])=[C:4]1[OH:5].Br[C:15]1[CH:16]=[C:17]([C@:21]23[CH2:29][O:28][CH2:27][C@H:26]2[CH2:25][S:24][C:23]([NH:30][C:31](=[O:38])[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[N:22]3)[CH:18]=[CH:19][CH:20]=1.C1(N)CCCCC1N.[N-:47]=[N+:48]=[N-:49].[Na+]>O.C(O)C.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[O:2]=[C:3]1[O:9][C@H:8]([C@H:10]([CH2:12][OH:13])[OH:11])[C:6]([OH:7])=[C:4]1[OH:5].[N:47]([C:15]1[CH:16]=[C:17]([C@:21]23[CH2:29][O:28][CH2:27][C@H:26]2[CH2:25][S:24][C:23]([NH:30][C:31](=[O:38])[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[N:22]3)[CH:18]=[CH:19][CH:20]=1)=[N+:48]=[N-:49]

Participants

9

Reactant 4

HCID 46101,2-DiaminocyclohexaneHCID 33557Sodium AzideHCID 57504889HCID 57504889, compoundHCID 66586226sodium L-ascorbic acid2×

Product 2

HCID 54670067L-Ascorbic AcidHCID 57504888HCID 57504888, compoundYield 81.7%

Reagents, catalysts & solvents 3

HCID 24463Copper sulfate pentahydrateCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

A 0.66 M solution of L-ascorbic acid is prepared by dissolving L-ascorbic acid sodium salt (0.79 g, 2.0 mmol) in water (6 mL). N-((4aS,7aS)-7a-(3-bromophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (1.40 g, 3.35 mmol) and 1,2-cyclohexanediamine, N,N′-dimethyl-, trans (+/−) (162 mg, 1.11 mmol) are dissolved in ethanol (13.4 mL). Sodium azide (0.661 g, 10.1 mmol) is added. The 0.66 M aqueous L-ascorbic acid sodium salt (2.24 mL) and water (2.58 mL) are added. The reaction flask is fitted with a reflux condenser and the mixture is degassed and evacuated with nitrogen. Copper (II) sulfate pentahydrate (0.184 g, 0.738 mmol) is added and the reaction flask is heated to 80° C. and stirred for 1.5 h. The reaction mixture is cooled to room temperature and ice water is added. The reaction mixture is extracted three times with ethyl acetate. The combined organic phase is dried over sodium sulfate and the solvent is removed under reduced pressure to give a residue that is purified on silica gel with 50% ethyl acetate in hexanes to give the title compound (0.620 g, 49%). Further elution of the flash column with 100% ethyl acetate yields more title compound (0.488 g, 41%). ES/MS m/e: 380 (M+1).

Workup

  1. customThe reaction flask is fitted with a reflux condenser
  2. customthe mixture is degassed
  3. customevacuated with nitrogen
  4. temperatureThe reaction mixture is cooled to room temperature
  5. extractionThe reaction mixture is extracted three times with ethyl acetate
  6. dry with materialThe combined organic phase is dried over sodium sulfate
  7. customthe solvent is removed under reduced pressure
  8. customto give a residue that
  9. customis purified on silica gel with 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-8a599bd329114e959fc3a6942d18e81e
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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