tert-butyl N-[(2S)-4-methyl-1-oxopentan-2-yl]carbamate → HCID 22843595, compound

HRID 1030522Notes

Reaction equation

HRID 1030522 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:14]=[O:15])[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[C:18]1[S:19][CH:20]=[CH:21][N:22]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>ClCCl.O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:10][CH:11]([CH3:12])[CH3:13])[C@@H:14]([C:18]1[S:19][CH:20]=[CH:21][N:22]=1)[OH:15])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 104275tert-butyl N-[(2S)-4-methyl-1-oxopentan-2-yl]carbamateHCID 5884532-TrimethylsilylthiazoleHCID 2724141Tetrabutylammonium Fluoride

Product 1

HCID 22843595HCID 22843595, compoundYield 4.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 10.8 g of t-butoxycarbonyl-L-leucinal in 40 of dichloromethane was added 9.4 g of 2-trimethylsilyl thiazole in 10 ml of dichloromethane. The reaction was allowed to stand for 48 hours, then was cooled in an ice bath and treated cautiously with 30 ml of 1M tetra-n-butylammonium fluoride in tetrahydrofuran. This mixture was refluxed for 1.5 hours and then concentrated to an oil. The oil was dissolved in 100 ml of ethyl acetate, washed with 50 ml each of 2N citric acid, 1M sodium bicarbonate and brine and dried. The solution was treated with activated carbon, filtered through a pad of hydrous magnesium silicate and concentrated to an oil. This oil was dissolved in 50 ml of 10% ethyl acetate in dichloromethane and chromatographed on two columns in the same solvent. Refractive index was monitored at S 20, 250 ml/minute. The main peak in hold-back volumes 6-10 was cut into 1 liter portions which were separately evaporated. The first three of these all crystallized and the solids were recrystallized form isopropyl ether and hexane, giving 0.7 g of (S)2-(t-butoxycarbonyl)amino-4-methyl-(S)1-(2-thiazolyl)pentan-1-ol as crystals, mp 121°-122° C.

Workup

  1. temperaturewas cooled in an ice bath
  2. temperatureThis mixture was refluxed for 1.5 hours
  3. concentrationconcentrated to an oil
  4. dissolutionThe oil was dissolved in 100 ml of ethyl acetate
  5. washwashed with 50 ml each of 2N citric acid, 1M sodium bicarbonate and brine
  6. customdried
  7. additionThe solution was treated with activated carbon
  8. filtrationfiltered through a pad of hydrous magnesium silicate
  9. concentrationconcentrated to an oil
  10. dissolutionThis oil was dissolved in 50 ml of 10% ethyl acetate in dichloromethane
  11. customchromatographed on two columns in the same solvent
  12. customwere separately evaporated
  13. customThe first three of these all crystallized
  14. customthe solids were recrystallized form isopropyl ether and hexane

Sources & evidence

ORD record
ord-d4e45fb2baef4f83b5f6bf26eb263b8a
Source dataset
uspto-grants-1992_04
Patent number
US05106835

Reaction notes

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