Diisopropylamine → HCID 178499310, compound

HRID 2099611Notes

Reaction equation

HRID 2099611 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][O:14][C:15]([C:17]1[S:18][CH:19]=[CH:20][C:21]=1[N:22]([CH:32]1[CH2:41][CH2:40][C:35]2([O:39][CH2:38][CH2:37][O:36]2)[CH2:34][CH2:33]1)[C:23]([C@H:25]1[CH2:30][CH2:29][C@H:28]([CH3:31])[CH2:27][CH2:26]1)=[O:24])=[O:16].[CH3:42][C:43]1([CH3:50])[CH2:48][CH2:47][C:46](=[O:49])[CH2:45][CH2:44]1>C1COCC1>[CH3:13][O:14][C:15]([C:17]1[S:18][C:19]([C:46]2([OH:49])[CH2:47][CH2:48][C:43]([CH3:50])([CH3:42])[CH2:44][CH2:45]2)=[CH:20][C:21]=1[N:22]([CH:32]1[CH2:41][CH2:40][C:35]2([O:39][CH2:38][CH2:37][O:36]2)[CH2:34][CH2:33]1)[C:23]([C@H:25]1[CH2:26][CH2:27][C@H:28]([CH3:31])[CH2:29][CH2:30]1)=[O:24])=[O:16]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 138166Cyclohexanone, 4,4-dimethyl-HCID 178418339ButyllithiumHCID 178499312HCID 178499312, compound

Product 1

HCID 178499310HCID 178499310, compoundYield 110.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

Diisopropylamine (5.75 g, 56.8 mmol) and dry THF (58 mL) were added to a dry 500 mL 3 neck round bottom flask under nitrogen. The solution was cooled to −40° C. and nBuLi (39 mL, 47.4 mmol) was added slowly while keeping the internal temperature at −40° C. After 15 min, a suspension of 3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbo-nyl)-amino]-thiophene-2-carboxylic acid methyl ester (10.0 g, 23.7 mmol) in THF (70 mL) was added dropwise while maintaining the internal temperature at −40° C. After 30 min at −40° C., 4,4-dimethyl-cyclohexanone (5.88 g, 47.7 mmol) was added in one portion and stirred at −40° C. for 30 min. The reaction mixture was quenched with saturated NH4Cl, partitioned and the aqueous phase extracted with EtOAc. The combined organic phase was washed with brine, dried over MgSO4, filtered and evaporated to obtain crude 3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-5-(1-hydroxy-4,4-dimethyl-cyclohexyl)-thiophene-2-carboxylic acid methyl ester (14.4 g) which was used for the next step without any purification.

Workup

  1. customat −40° C
  2. additionwas added dropwise
  3. temperaturewhile maintaining the internal temperature at −40° C
  4. waitAfter 30 min at −40° C.
  5. customThe reaction mixture was quenched with saturated NH4Cl
  6. custompartitioned
  7. extractionthe aqueous phase extracted with EtOAc
  8. washThe combined organic phase was washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-2826051a987c48858b4a6fe54175caa3
Source dataset
uspto-grants-2009_08
Patent number
US07569600B2

Reaction notes

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