Triethylamine → (1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-{[(3,4-difluorophenyl)sulfanyl]methyl}-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid

HRID 469923Notes

Reaction equation

HRID 469923 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13](ON=C(C1C=CC=CC=1)C#N)=[O:14])([CH3:11])([CH3:10])[CH3:9].[NH2:26][C@@:27]1([C:47]([OH:49])=[O:48])[C@H:32]([CH2:33][S:34][C:35]2[CH:40]=[CH:39][C:38]([F:41])=[C:37]([F:42])[CH:36]=2)[C@@H:31]([OH:43])[C@@H:30]2[C@H:28]1[C@H:29]2[C:44]([OH:46])=[O:45]>O1CCOCC1.O>[C:8]([O:12][C:13]([NH:26][C@@:27]1([C:47]([OH:49])=[O:48])[C@H:32]([CH2:33][S:34][C:35]2[CH:40]=[CH:39][C:38]([F:41])=[C:37]([F:42])[CH:36]=2)[C@@H:31]([OH:43])[C@@H:30]2[C@H:28]1[C@H:29]2[C:44]([OH:46])=[O:45])=[O:14])([CH3:11])([CH3:10])[CH3:9]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 938652-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrileHCID 69669747LY-3020371

Product 1

HCID 69669731(1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-{[(3,4-difluorophenyl)sulfanyl]methyl}-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acidYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Triethylamine (407.27 mL, 2.92 mol) and [2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile] (308.39 g, 1.25 mol) are added to a suspension of (1S,2R,3S,4S,5R,6R)-2-amino-3-{[(3,4-difluorophenyl)sulfanyl]methyl}-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid (300.00 g, 834.84 mmol) in 1,4-dioxane (500.9 mL) and water (500.9 mL) at 25° C. The mixture is warmed to 50° C. After 12 hours, the reaction is cooled to 25° C., diluted with water (2.5 L), and washed with methyl tert-butyl ether (6×1 L). Basify the aqueous phase with a solution of aqueous. 1N HCl until pH=2, and extract with ethyl acetate (3×2 L). The combined ethyl acetate extracts are washed with brine, dried over MgSO4, and concentrated in vacuo to yield the title compound (250 g, 65% yield). MS (m/z): 360 (M+-Boc).

Workup

  1. temperaturethe reaction is cooled to 25° C.
  2. washwashed with methyl tert-butyl ether (6×1 L)
  3. extraction1N HCl until pH=2, and extract with ethyl acetate (3×2 L)
  4. washThe combined ethyl acetate extracts are washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-87f510c11702437fa3ea28f25a6c3dc4
Source dataset
uspto-grants-2014_01
Patent number
US08629169B2

Reaction notes

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