Trimethylphosphine → HCID 131734123, compound

HRID 716174Notes

Reaction equation

HRID 716174 reaction equation
[N:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[N:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:11]1)=C=S.N(C1C=NC=CC=1N1CCC[C@H](NC(=O)OC(C)(C)C)C1)=[N+]=[N-].[P:47]([CH3:50])([CH3:49])[CH3:48]>C1COCC1>[CH3:48][P:47](=[N:1][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[N:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:11]1)([CH3:50])[CH3:49]

Participants

5

Reactant 3

HCID 68983TrimethylphosphineHCID 89183171HCID 89183171, compoundHCID 131734124HCID 131734124, compound

Product 1

HCID 131734123HCID 131734123, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

tert-butyl ((3S)-1-(3-isothiocyanato-4-pyridinyl)-3-piperidinyl)carbamate. A dry, 3 neck, 100 mL Morton flask was configured as follows: opening 1: septa/Ar inlet; opening 2 (center): septa/PTFE addition needle; opening 3: septa. The flask was charged with tert-butyl ((3S)-1-(3-azido-4-pyridinyl)-3-piperidinyl)carbamate (3.25 g, 10.22 mmol), a stirbar, and dry THF (10 mL). The slurry was stirred for 10 min, and immersed into an ice-water bath. A syringe charged with 1.0 M PMe3 in THF (10.73 mL, 10.73 mmol, Aldrich) was fitted to the PTFE addition needle and added over a 15 min period via a syringe pump. The reaction was stirred for 15 min. The solution was charged to a dry 50 mL glass syringe via the PTFE addition needle to afford (S)-tert-butyl (1-(3-((trimethylphosphoranylidene)amino)pyridin-4-yl)piperidin-3-yl)carbamate. A dry, 250 mL, one neck round bottom flask was charged with dry THF (16 mL), carbon disulfide (6.17 mL, 102 mmol) and a stirbar. The flask was fitted with a septa/Ar inlet, and immersed into an ice-water bath. The solution was stirred for 15 min. The septa was pierced with the PTFE addition needle fitted to the 50 mL glass syringe containing the solution of (S)-tert-butyl (1-(3-((trimethylphosphoranylidene)amino)pyridin-4-yl)piperidin-3-yl)carbamate and the solution (19 mL) was added via syringe pump over a 1 h period. The reaction was stirred an additional 10 min and the solvent was removed in vacuo. The residue was further dried at <1 mm Hg at RT to afford tert-butyl ((3S)-1-(3-isothiocyanato-4-pyridinyl)-3-piperidinyl)carbamate. MS (ESI, pos. ion) m/z: 335.0 [M+H].

Workup

  1. customimmersed into an ice-water bath
  2. additionadded over a 15 min period via a syringe pump
  3. stirringThe reaction was stirred for 15 min

Sources & evidence

ORD record
ord-a4d491f1f92a4d7a9dbb74ab71824374
Source dataset
uspto-grants-2015_11
Patent number
US09187486B2

Reaction notes

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