Ammonium Chloride → tert-Butyl 3-[2-(tert-butyldiphenylsilanyloxy)ethyl]-6-(3-isobutylcyclobutyl)-4-oxo-5-hexynoate

HRID 1912051Notes

Reaction equation

HRID 1912051 reaction equation
Br[C:2](Br)=[CH:3][CH:4]1[CH2:7][CH:6]([CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:5]1.C([Li])CCC.[Si:18]([O:35][CH2:36][CH2:37][CH:38]([C:47](=[O:52])NCOC)[CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])([C:31]([CH3:34])([CH3:33])[CH3:32])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[Cl-].[NH4+]>O1CCCC1.O>[Si:18]([O:35][CH2:36][CH2:37][CH:38]([C:47](=[O:52])[C:2]#[C:3][CH:4]1[CH2:7][CH:6]([CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:5]1)[CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])([C:31]([CH3:32])([CH3:34])[CH3:33])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 71114767tert-Butyl 5-(tert-butyldiphenylsilanyloxy)-3-methoxymethylcarbamoylvalerateHCID 866750331-(2,2-Dibromovinyl)-3-isobutylcyclobutaneHCID 178418339Butyllithium

Product 1

HCID 71127321tert-Butyl 3-[2-(tert-butyldiphenylsilanyloxy)ethyl]-6-(3-isobutylcyclobutyl)-4-oxo-5-hexynoateYield 96.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

1-(2,2-Dibromovinyl)-3-isobutylcyclobutane (40 g) and tetrahydrofuran (280 mL) were mixed. To the mixture was added n-butyllithium (2.66 M in hexane) (104 mL) dropwise at −78° C. The mixture was stirred at ice temperature and a solution of tert-butyl 5-(tert-butyldiphenylsilanyloxy)-3-methoxymethylcarbamoylvalerate (54 g) in tetrahydrofuran (100 mL) was added dropwise to the mixture. After stirring at ice temperature for 1 hr, saturated aqueous ammonium chloride (180 mL) and water (100 mL) were added to the reaction mixture. The mixture was extracted with ethyl acetate (600 mL), washed with saturated aqueous ammonium chloride (180 mL and 400 mL) and dried over sodium sulfate. The sodium sulfate was filtered off and the filtrate was concentrated in vacuo. After an addition of silica gel (90 g) and ethyl acetate/hexane=1/20 (600 mL) into the resultant residue, the mixture was stirred at RT for 1 hr. The silica gel was filtered off and the filtrate was concentrated in vacuo to give the title compound (60.09 g) as a crude product.

Workup

  1. stirringAfter stirring at ice temperature for 1 hr
  2. extractionThe mixture was extracted with ethyl acetate (600 mL)
  3. washwashed with saturated aqueous ammonium chloride (180 mL and 400 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationThe sodium sulfate was filtered off
  6. concentrationthe filtrate was concentrated in vacuo
  7. additionAfter an addition of silica gel (90 g) and ethyl acetate/hexane=1/20 (600 mL) into the resultant residue
  8. stirringthe mixture was stirred at RT for 1 hr
  9. filtrationThe silica gel was filtered off
  10. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-7573f9e280e54c9db91176c4719b9e58
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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