Sodium Chloride → 1-Piperidinecarboxylic acid, 3-(2-thiazolylcarbonyl)-, 1,1-dimethylethyl ester, (3S)-

HRID 714763Notes

Reaction equation

HRID 714763 reaction equation
C([Li])CCC.[S:6]1[CH:10]=[CH:9][N:8]=[CH:7]1.COCN[C:15]([C@H:17]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]1)=[O:16].[Cl-].[Na+]>O1CCCC1.O>[S:6]1[CH:10]=[CH:9][N:8]=[C:7]1[C:15]([C@H:17]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]1)=[O:16]

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 9256ThiazoleHCID 97416691HCID 97416691, compoundHCID 178418339Butyllithium

Product 1

HCID 895852361-Piperidinecarboxylic acid, 3-(2-thiazolylcarbonyl)-, 1,1-dimethylethyl ester, (3S)-Yield 88.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

136.6 g (0.32 mol) of n-butyllithium (15% in n-hexane) were added dropwise at −68° C. to a solution of 25 g (0.291 mol) of thiazole in 1 l of tetrahydrofuran. The mixture was warmed to 0° C. and subsequently cooled to −40° C. This mixture was then added dropwise to a solution of 79.2 g (0.291 mol) of tert-butyl (S)-3-(methoxymethylcarbamoyl)piperidine-1-carboxylate in 1.4 l of tetrahydrofuran at −50° C. The reaction mixture was then slowly warmed to 0° C., and 2 l of ice-water were added. After addition of 2 l of water and 2 l of saturated sodium chloride solution, the crude mixture was extracted with a total of 4 l of ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over sodium sulfate and evaporated. The crude product (87 g) was chromatographed over a silica-gel column, giving 76.4 g of tert-butyl (S)-3-(thiazole-2-carbonyl)piperidine-1-carboxylate as brown resin; rotation value in methanol [α]20D=+27.4°; 1H NMR (500 MHz, DMSO) δ 8.22 (d, J=3.0, 1H), 8.17 (d, J=3.0, 1H), 4.22-3.86 (m, 1H), 3.84-3.69 (m, 2H), 3.60-3.52 (m, 1H), 3.20-3.05 (m, 1H), 2.08-1.92 (m, 2H), 1.89-1.60 (m, 2H), 1.35 (s, 9H).

Workup

  1. temperaturesubsequently cooled to −40° C
  2. temperatureThe reaction mixture was then slowly warmed to 0° C.
  3. extractionthe crude mixture was extracted with a total of 4 l of ethyl acetate
  4. washThe organic phase was washed with saturated sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe crude product (87 g) was chromatographed over a silica-gel column

Sources & evidence

ORD record
ord-8cb9622ad3bd4bc591733bebb3f6cfc1
Source dataset
uspto-grants-2015_11
Patent number
US09187469B2

Reaction notes

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