Hydrochloric Acid → LY3020371 (hydrochloride)

HRID 469915Notes

Reaction equation

HRID 469915 reaction equation
C(OC([NH:8][C@@:9]1([C:33]([O:35]C(C)(C)C)=[O:34])[C@H:14]([CH2:15][S:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[CH:18]=2)[C@@H:13]([OH:25])[C@@H:12]2[C@H:10]1[C@H:11]2[C:26]([O:28]C(C)(C)C)=[O:27])=O)(C)(C)C.[ClH:40]>ClCCl>[ClH:40].[NH2:8][C@@:9]1([C:33]([OH:35])=[O:34])[C@H:14]([CH2:15][S:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[CH:18]=2)[C@@H:13]([OH:25])[C@@H:12]2[C@H:10]1[C@H:11]2[C:26]([OH:28])=[O:27]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67637733HCID 67637733, compound

Product 1

HCID 69669746LY3020371 (hydrochloride)

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

Di-tert-butyl (1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-{[(3,4-difluorophenyl)sulfanyl]methyl}-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate (4.11 g, 7.19 mmol) is weighed into a one liter round bottom with a stirring bar. Hydrogen chloride (4N in dioxane, 120 mL, 480.0 mmol) is added. The mixture is warmed to 70° C. for 2 hours and then allowed to cool to ambient temperature. The solvent is removed under reduced pressure to give a residue. The residue is dissolve in dichloromethane (200 mL) and the solvent is removed under reduced pressure to give a residue. This is repeated two more times to give (1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride. This material is taken up in tetrahydrofuran (100 mL) as a suspension. To this suspension is added triethylamine (40.08 mL, 287.57 mmol). The suspension is stirred for 10 minutes and then methanol (50 ml) is added. To the reaction is added di-t-butyldicarbonate (4.71 g, 21.57 mmol) and the mixture is heated to 80° C. for 2 hours. The mixture is allowed to come to ambient temperature and the solvent is removed under reduced pressure to give a residue. The residue is dissolved in acetonitrile (50 ml), transferred to a separatory funnel and washed with hexanes. The acetonitrile layer is separated and removed under reduced pressure to give a residue. The residue is suspended in diethyl ether, transferred to a separatory funnel, washed with 1 N aqueous HCl, dried over magnesium sulfate, filtered, and concentrated under reduced pressure giving the title compound (3 g, 6.53 mmol, 90.82% yield). MS (m/z): 457.8 (M−H).

Workup

  1. temperatureto cool to ambient temperature
  2. customThe solvent is removed under reduced pressure
  3. customto give a residue
  4. customthe solvent is removed under reduced pressure
  5. customto give a residue

Sources & evidence

ORD record
ord-64294117f3104c09bcc0121c69b30ff5
Source dataset
uspto-grants-2014_01
Patent number
US08629169B2

Reaction notes

Loading…