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

HRID 1053489Notes

Reaction equation

HRID 1053489 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 58113947(R)-4-methylcyclohex-3-enecarbonyl 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 583604645-(3,3-Dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1R)-4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl esterYield 67%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
90 °C

Procedure

(R)-4-methylcyclohex-3-enecarbonyl chloride 504 (2.65 mmol), 5-(3,3-dimethyl-but-1-ynyl)-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester 505 (250 mg, 0.66 mmol) and potassium phosphate tribasic (562 mg, 2.65 mmol) were suspended in dichloroethane (1.7 mL), sealed with a cap and heated to 90° C. After 16 hours, 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 (10-40% EtOAc:Hexanes) afforded 220 mg (67% yield) of the desired 5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-((1R)-4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester 506 as a beige 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-296b7ec853e745ef95d169a8136ed185
Source dataset
uspto-grants-2016_07
Patent number
US09393256B2

Reaction notes

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