Hydrochloric Acid → 5-(3,3-Dimethyl-but-1-ynyl)-3-[(4-methyl-cyclohex-3-enecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester

HRID 1046459Notes

Reaction equation

HRID 1046459 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:30]#[C:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[CH:8][C:9]=1[N:10]([CH:20]1[CH2:29][CH2:28][C:23]2(OCC[O:24]2)[CH2:22][CH2:21]1)[C:11]([CH:13]1[CH2:18][CH2:17][C:16]([CH3:19])=[CH:15][CH2:14]1)=[O:12])=[O:4].Cl.CO>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:30]#[C:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[CH:8][C:9]=1[N:10]([C:11]([CH:13]1[CH2:18][CH2:17][C:16]([CH3:19])=[CH:15][CH2:14]1)=[O:12])[CH:20]1[CH2:21][CH2:22][C:23](=[O:24])[CH2:28][CH2:29]1)=[O:4]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 887Methanol2×HCID 581141185-(3,3-Dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 668498835-(3,3-Dimethyl-but-1-ynyl)-3-[(4-methyl-cyclohex-3-enecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl esterYield 106.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

5-(3,3-Dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (240 mg, 0.48 mmol) was dissolved in THF (3.2 mL) and treated with 4M HCl (1.6 mL, 0.8 mmol). The reaction mixture was heated to 45° C. and stirred at ambient temperature. After 2 h, methanol was added (15-20 drops) and the solution was stirred for 3 h. An additional portion of 4M HCl (1.6 mL, 0.8 mmol) and methanol (1 mL) were added and the solution was stirred 16 h at ambient temperature followed by 40° C. for 4 h. The solution was partitioned between water and ethyl acetate. The organic layer was washed with sodium bicarbonate (sat. aq.) and brine, dried over sodium sulfate and concentrated to 233 mg (quantitative yield) of the desired 5-(3,3-dimethyl-but-1-ynyl)-3-[(4-methyl-cyclohex-3-enecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester as a white foam.

Workup

  1. stirringthe solution was stirred for 3 h
  2. stirringthe solution was stirred 16 h at ambient temperature
  3. waitfollowed by 40° C. for 4 h
  4. customThe solution was partitioned between water and ethyl acetate
  5. washThe organic layer was washed with sodium bicarbonate (sat. aq.) and brine
  6. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-f267a66d247e4ce8b8def9cfa0f0d649
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

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