Water → HCID 178461278, compound

HRID 1189999Notes

Reaction equation

HRID 1189999 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH2:32][CH2:31][CH:30]([O:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].[Li+].[OH-].O>C1COCC1.O.CO>[OH:26][C@H:23]1[CH2:24][CH2:25][C@H:20]([N:10]([C:11]([C@H:13]2[CH2:14][CH2:15][C@H:16]([CH3:19])[CH2:17][CH2:18]2)=[O:12])[C:9]2[CH:8]=[C:7]([C:27]3[CH2:32][CH2:31][CH:30]([O:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH2:29][CH:28]=3)[S:6][C:5]=2[C:3]([OH:4])=[O:2])[CH2:21][CH2:22]1

Participants

5

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 178499304HCID 178499304, compound

Product 1

HCID 178461278HCID 178461278, compoundYield 11.2%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-5-(4-phenoxy-cyclohex-1-enyl)-thiophene-2-carboxylic acid methyl ester (30 mg, 0.05 mmol) in THF: H2O: MeOH (3:1:2) (2 mL), was added LiOH in water (1N) (0.2 mL, 0.2 mmol). The reaction mixture was stirred at 70° C. for 4 h. The reaction mixture was concentrated under reduced pressure on a rotary evaporator. The mixture was partitioned between ethyl acetate and water. The water layer was acidified using 0.1 N HCl. The EtOAc layer was separated and dried over Na2SO4. Filtration and removal of the solvent under reduced pressure on a rotary evaporator followed by HPLC purification afforded 3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-5-(4-phenoxy-cyclohex-1-enyl)-thiophene-2-carboxylic acid (3 mg, 10%) as a foam.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure on a rotary evaporator
  2. customThe mixture was partitioned between ethyl acetate and water
  3. customThe EtOAc layer was separated
  4. dry with materialdried over Na2SO4
  5. filtrationFiltration and removal of the solvent under reduced pressure
  6. customon a rotary evaporator
  7. customfollowed by HPLC purification

Sources & evidence

ORD record
ord-3deacc4c48d44729b32e8db5d7410e3b
Source dataset
uspto-grants-2014_03
Patent number
US08674118B2

Reaction notes

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