Ethyl Acetate → 5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1S)-4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

HRID 632556Notes

Reaction equation

HRID 632556 reaction equation
[CH3:1][C:2]1[CH2:7][CH2:6][C@H:5]([C:8](Cl)=[O:9])[CH2:4][CH:3]=1.[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([C:31]#[C:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:18][C:19]=1[NH:20][CH:21]1[CH2:30][CH2:29][C:24]2([O:28][CH2:27][CH2:26][O:25]2)[CH2:23][CH2:22]1)=[O:14].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CCOC(C)=O>ClC(Cl)C>[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([C:31]#[C:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:18][C:19]=1[N:20]([CH:21]1[CH2:30][CH2:29][C:24]2([O:28][CH2:27][CH2:26][O:25]2)[CH2:23][CH2:22]1)[C:8]([C@H:5]1[CH2:6][CH2:7][C:2]([CH3:1])=[CH:3][CH2:4]1)=[O:9])=[O:14]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 12951476(1S)-4-Methylcyclohex-3-ene-1-carbonyl chlorideHCID 581141495-(3,3-Dimethyl-but-1-ynyl)-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 673215985-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1S)-4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
90 °C

Procedure

(1S)-4-Methyl-cyclohex-3-enecarboxylic acid chloride (1.5 mmol), 5-(3,3-dimethyl-but-1-ynyl)-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester (159 mg, 0.42 mmol) and potassium phosphate tribasic (266 mg, 1.25 mmol) was suspended in dichloroethane (1 mL), sealed with a cap and heated to 90° C. After 16 h, the reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was separated and the aqueous extracted again with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. Flash chromatography (15-60% EtOAc:Hexanes) afforded 128 mg (61% yield) of the desired 5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1S)-4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester as a white foam.

Workup

  1. customsealed with
  2. customa cap
  3. temperaturethe reaction mixture was cooled
  4. custompartitioned between ethyl acetate and water
  5. customThe organic layer was separated
  6. extractionthe aqueous extracted again with ethyl acetate
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-40f8183a2cc446d7ad2a76a06c19d517
Source dataset
uspto-grants-2016_04
Patent number
US09321753B2

Reaction notes

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