Oxalyl chloride → HCID 58114143, compound

HRID 401839Notes

Reaction equation

HRID 401839 reaction equation
[CH3:1][C:2]1[CH2:7][C@H:6]([CH3:8])[C@@H:5]([C:9]([OH:11])=O)[CH2:4][CH:3]=1.C(Cl)(C(Cl)=O)=O.[CH3:18][C:19]([CH3:39])([CH3:38])[C:20]#[C:21][C:22]1[S:26][CH:25]=[C:24]([NH:27][CH:28]2[CH2:37][CH2:36][C:31]3([O:35][CH2:34][CH2:33][O:32]3)[CH2:30][CH2:29]2)[CH:23]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.ClCCCl.CN(C=O)C>[CH3:18][C:19]([CH3:39])([CH3:38])[C:20]#[C:21][C:22]1[S:26][CH:25]=[C:24]([N:27]([CH:28]2[CH2:37][CH2:36][C:31]3([O:32][CH2:33][CH2:34][O:35]3)[CH2:30][CH2:29]2)[C:9]([C@@H:5]2[C@@H:6]([CH3:8])[CH2:7][C:2]([CH3:1])=[CH:3][CH2:4]2)=[O:11])[CH:23]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 45084801HCID 45084801, compoundHCID 58114044HCID 58114044, compound

Product 1

HCID 58114143HCID 58114143, compoundYield 92.3%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

(1S,6S)-4,6-Dimethyl-cyclohex-3-ene-carboxylic acid (3.04 g, 19.7 mmol) was dissolved in CH2Cl2 (30 mL) and DMF (20 μL) was added. The solution was cooled to 0° C. and then (COCl)2 (3.7 mL, 39 mmol) was added slowly. The reaction was stirred in an ice bath for 2 hours and then concentrated. The residue was taken up in hexanes and concentrated; this hexanes coevaporation was repeated once more. To the residue was added [5-(3,3-dimethyl-but-1-ynyl)-thiophen-3-yl]-(1,4-dioxa-spiro[4.5]dec-8-yl)-amine (4.16 g, 13 mmol), diisopropylethylamine (4.5 mL, 26 mmol), and 1,2-dichloroethane (40 mL) at 0° C. The solution was warmed to room temperature and stirred overnight. The reaction was diluted with CH2Cl2, twice washed with saturated NH4Cl (aq), dried over MgSO4, filtered, concentrated, and purified by silica gel column chromatography, eluting with a mixture of 0-75% EtOAc/hexanes, to give (1S,6S)-4,6-dimethyl-cyclohex-3-ene-carboxylic acid [5-(3,3-dimethyl-but-1-ynyl)-thiophen-3-yl]-(1,4-dioxa-spiro[4.5]dec-8-yl)-amide (5.6 g, 12 mmol) as a single isomer.

Workup

  1. concentrationconcentrated
  2. concentrationconcentrated
  3. temperatureThe solution was warmed to room temperature
  4. stirringstirred overnight
  5. washtwice washed with saturated NH4Cl (aq)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by silica gel column chromatography
  10. washeluting with a mixture of 0-75% EtOAc/hexanes

Sources & evidence

ORD record
ord-3b358f7bd7844c318128de860312677b
Source dataset
uspto-grants-2014_06
Patent number
US08741946B2

Reaction notes

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