Water → HCID 178499267, compound

HRID 73223Notes

Reaction equation

HRID 73223 reaction equation
[OH2:1].[CH3:2][O:3][C:4]([C:6]1[S:7][C:8]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:9][C:10]=1[N:11]([C:19]([CH:21]1[CH2:26][CH2:25][CH:24]([CH3:27])[CH2:23][CH2:22]1)=[O:20])[CH:12]1[CH2:17][CH2:16][C:15](=[CH2:18])[CH2:14][CH2:13]1)=[O:5].[OH-].[Na+].[BH4-].[Na+]>O1CCCC1>[CH3:2][O:3][C:4]([C:6]1[S:7][C:8]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:9][C:10]=1[N:11]([CH:12]1[CH2:17][CH2:16][C:15]([OH:1])([CH3:18])[CH2:14][CH2:13]1)[C:19]([C@H:21]1[CH2:26][CH2:25][C@@H:24]([CH3:27])[CH2:23][CH2:22]1)=[O:20])=[O:5].[CH3:2][O:3][C:4]([C:6]1[S:7][C:8]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:9][C:10]=1[N:11]([CH:12]1[CH2:17][CH2:16][C:15]([OH:1])([CH3:18])[CH2:14][CH2:13]1)[C:19]([C@H:21]1[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]1)=[O:20])=[O:5]

Participants

7

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 59752338HCID 59752338, compound

Product 2

HCID 178499266HCID 178499266, compoundHCID 178499267HCID 178499267, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of water (1 mL) and tetrahydrofuran (1 mL) was added mercuric acetate (83.0 mg, 0.277 mmol, 1 eq) at room temperature. After stirring 10 min, the yellow solution was cooled to 0° C. and a solution of 3-[(4-Methyl-cyclohexanecarbonyl)-(4-methylene-cyclohexyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (125 mg, 0.277 mmol, 1 eq) was added dropwise. The resulting mixture was stirred 1 h at 0° C. NaOH 3M (1 mL) was then added, followed by sodium borohydride (10.0 mg, 0.277 mmol, 1 eq) and the reaction mixture was stirred 15 min at room temperature. The reaction mixture was extracted with dichloromethane (3×30 mL). Organic phases were combined, dried over sodium sulfate and concentrated. The crude was purified by chromatography (50% ethyl acetate/hexanes) and diastereoisomers were separated to give 90 mg of cis-3-[(4-Hydroxy-4-methyl-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester and 6.5 mg of trans-3-[(4-Hydroxy-4-methyl-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (74%), both as a white solid. cis-3-[(4-Hydroxy-4-methyl-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester. NMR 1H (CDCl3, 400 MHz): 7.63 ppm (d, 2H); 7.40 ppm (m, 3H); 6.98 ppm (s, 1H); 4.50 ppm (tt, 1H); 3.85 ppm (s, 3H); 2.00 ppm (m, 1H); 1.80-1.20 ppm (m, 15H); 1.18 ppm (s, 3H); 0.78 ppm (d, 3H); 0.64 ppm (m, 2H).

Workup

  1. stirringThe resulting mixture was stirred 1 h at 0° C
  2. stirringthe reaction mixture was stirred 15 min at room temperature
  3. extractionThe reaction mixture was extracted with dichloromethane (3×30 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude was purified by chromatography (50% ethyl acetate/hexanes) and diastereoisomers
  7. customwere separated

Sources & evidence

ORD record
ord-f947fce7ef234512bd882bebb1055e91
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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