Methyl chloroformate → Tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-((methoxycarbonyl)oxy)piperidine-1-carboxylate

HRID 514848Notes

Reaction equation

HRID 514848 reaction equation
[Si:1]([O:8][CH2:9][C:10]#[C:11][C:12]1([OH:25])[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li]CCCC.[C:31](Cl)(=[O:34])[O:32][CH3:33]>C1COCC1>[C:21]([O:20][C:18]([N:15]1[CH2:16][CH2:17][C:12]([C:11]#[C:10][CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])([O:25][C:31]([O:32][CH3:33])=[O:34])[CH2:13][CH2:14]1)=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 90418995Tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-hydroxypiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 90418921Tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-((methoxycarbonyl)oxy)piperidine-1-carboxylateYield 78.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of tert-butyl 4-(3-((tert-butyldimethylsilyl)oxy)prop-1-yn-1-yl)-4-hydroxypiperidine-1-carboxylate (500 mg, 1.353 mmol) in 30 mL of anhydrous THF was added dropwise n-BuLi (0.65 mL, 1.623 mmol) at −78° C. under N2. After stirring for 1 h at −78° C., methyl carbonochloridate (176.2 mg, 1.623 mmol) in THF (1 mL) was added dropwise to the above solution at −78° C. under N2. The resulting mixture was stirred at −78° C. under N2 for 2 h, then allowed to warm to r.t. and stirred for another 8 h. The reaction mixture was cooled to −78° C. and quenched by sat. NH4Cl aq., and the resulting mixture was extracted with EtOAc (50 mL, 30 mL). The combined organic phase was washed with brine, dried over anhy. Na2SO4 and concentrated in vacuo. Column chromatography (15% PE/EtOAc) afforded 453 mg of title compound. 1H NMR (CHLOROFORM-d) δ: 4.40 (s, 2H), 4.26-4.15 (m, 2H), 3.80-3.67 (m, 2H), 3.41-3.28 (m, 2H), 2.27-2.14 (m, 2H), 2.00 (ddd, J=13.1, 9.2, 3.9 Hz, 2H), 1.48 (s, 9H), 1.33 (t, J=7.1 Hz, 4H), 0.92 (s, 9H), 0.14 (s, 6H).

Workup

  1. stirringThe resulting mixture was stirred at −78° C. under N2 for 2 h
  2. temperatureto warm to r.t.
  3. stirringstirred for another 8 h
  4. temperatureThe reaction mixture was cooled to −78° C.
  5. customquenched by sat. NH4Cl aq.
  6. extractionthe resulting mixture was extracted with EtOAc (50 mL, 30 mL)
  7. washThe combined organic phase was washed with brine
  8. customdried over anhy
  9. concentrationNa2SO4 and concentrated in vacuo

Sources & evidence

ORD record
ord-f385807448fe4a8fa8193f0f95439f87
Source dataset
uspto-grants-2015_08
Patent number
US09108921B2

Reaction notes

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