Thiazole → Carbamic acid, [(1S)-1-(hydroxy-2-thiazolylmethyl)-3-methylbutyl]-, 1,1-dimethylethyl ester

HRID 476799Notes

Reaction equation

HRID 476799 reaction equation
C([Li])CCC.[S:6]1[CH:10]=[CH:9][N:8]=[CH:7]1.[CH3:11][C:12]([CH3:25])([O:14][C:15]([NH:17][C@H:18]([CH:23]=[O:24])[CH2:19][CH:20]([CH3:22])[CH3:21])=[O:16])[CH3:13]>CCCCCC.O1CCCC1>[CH3:13][C:12]([CH3:25])([O:14][C:15]([NH:17][C@@H:18]([CH2:19][CH:20]([CH3:21])[CH3:22])[CH:23]([C:7]1[S:6][CH:10]=[CH:9][N:8]=1)[OH:24])=[O:16])[CH3:11]

Participants

6

Reactant 3

HCID 9256ThiazoleHCID 104275tert-butyl N-[(2S)-4-methyl-1-oxopentan-2-yl]carbamateHCID 178418339Butyllithium

Product 1

HCID 14796005Carbamic acid, [(1S)-1-(hydroxy-2-thiazolylmethyl)-3-methylbutyl]-, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

2.5 n-Butyllithium in hexane (8 ml.) is added to a solution containing thiazole (1.7 g., 20 mmole) in dry tetrahydrofuran (60 ml.) cooled to -70° under argon. After stirring a short time, the solid material begins to come out of solution. The reaction remains heterogeneous after 35 minutes at -40° to -35° . After cooling the reaction to -50° , a solution containing N-[(1,1-dimethylethoxy)carbonyl]-L-leucinal (2.2g., 10 mmole) in tetrahydrofuran (5 ml.) is added. After 90 minutes the reaction is warmed to -10° and quenched with saturated ammonium chloride (10 ml.). The reaction mixture is extracted into ether and the organic extract is rinsed with water and brine, dired (MgSO4) and concentrated in vacuo to give 1.8 g. of amide product. Two flash chromatographies on first 100 g. and then 150 g. of silica gel (LPS-1) eluting with petroleum ether:acetone (20:1 ) fails to remove a minor impurity from the co-eluting desired diastereimeric product mixture. A total of 1.2 g. of (2S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methyl-1-(2-thiazolyl)-1-pentanol is obtained. TLC (silica gel; petroleum ether:acetone, 4:1) Rf =0.37. 8 α]D =-38.6° (c=1, chloroform).

Workup

  1. temperaturecooled to -70° under argon
  2. temperatureAfter cooling
  3. customthe reaction to -50°
  4. additionis added
  5. temperatureAfter 90 minutes the reaction is warmed to -10°
  6. customquenched with saturated ammonium chloride (10 ml.)
  7. extractionThe reaction mixture is extracted into ether
  8. extractionthe organic extract
  9. washis rinsed with water and brine, dired (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customto give 1.8 g
  12. washof silica gel (LPS-1) eluting with petroleum ether:acetone (20:1 )
  13. customto remove a minor impurity from the co-eluting desired diastereimeric product mixture

Sources & evidence

ORD record
ord-2604f62e76e74de290b636ec2a829091
Source dataset
uspto-grants-1989_12
Patent number
US04885292

Reaction notes

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