Triethylamine → di-tert-butyl (1S,2R,3S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-{[(3,4-difluorophenyl)sulfanyl]methyl}-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylate

HRID 469921Notes

Reaction equation

HRID 469921 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:14](=[CH2:15])[C:13](=[O:16])[C@@H:12]2[C@H:10]1[C@H:11]2[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:31][C:32]1[CH:33]=[C:34]([SH:39])[CH:35]=[CH:36][C:37]=1[F:38].C(N(CC)CC)C>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][C@@:9]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@H:14]([CH2:15][S:39][C:34]2[CH:35]=[CH:36][C:37]([F:38])=[C:32]([F:31])[CH:33]=2)[C:13](=[O:16])[C@@H:12]2[C@H:10]1[C@H:11]2[C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27783783,4-DifluorobenzenethiolHCID 67643282Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-methylene-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate

Product 1

HCID 67646041di-tert-butyl (1S,2R,3S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-{[(3,4-difluorophenyl)sulfanyl]methyl}-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylateYield 141%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of di-tert-butyl (1S,2R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-methylidene-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylate (350.00 g, 826.43 mmol) in toluene (2.95 L) is treated with 3,4-difluorobenzenethiol (172.49 g, 1.18 mol) and triethylamine (205.61 mL, 149.28 g, 1.48 mol) at 25° C. The mixture is stirred at 80° C. After twelve hours, the reaction was cooled to room temperature, washed sequentially with 2N aqueous NaOH (pH=10) and aqueous. 1N HCl (pH=4), dried over MgSO4, and concentrated in vacuo to yield a residue. Triturate the residue with hexane (1 L) and remove the solvent to yield the title compound (664 g, 100% yield).

Workup

  1. waitAfter twelve hours
  2. temperaturethe reaction was cooled to room temperature
  3. washwashed sequentially with 2N aqueous NaOH (pH=10)
  4. dry with material1N HCl (pH=4), dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto yield a residue
  7. customTriturate the residue with hexane (1 L)
  8. customremove the solvent

Sources & evidence

ORD record
ord-ae24305f2d7e43fd8b7cc3212bf21f70
Source dataset
uspto-grants-2014_01
Patent number
US08629169B2

Reaction notes

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