Isopropyl chloroformate → HCID 59177770, compound

HRID 423601Notes

Reaction equation

HRID 423601 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]([CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[CH3:19])=[CH:13][N:12]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(N(C(C)C)CC)(C)C.Cl[C:36]([O:38][CH:39]([CH3:41])[CH3:40])=[O:37]>C(Cl)Cl.C1COCC1>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[CH:13][C:14]([O:17][CH:18]([CH:20]3[CH2:25][CH2:24][N:23]([C:36]([O:38][CH:39]([CH3:41])[CH3:40])=[O:37])[CH2:22][CH2:21]3)[CH3:19])=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)(=[O:3])=[O:4]

Participants

6

Reactant 3

HCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 66673312HCID 66673312, compound

Product 1

HCID 59177770HCID 59177770, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (±)-2-[4-(methylsulfonyl)phenyl]-5-{[1-(4-piperidinyl)ethyl]oxy}pyridine (0.27 g, 0.75 mmol) in CH2Cl2 (10 mL) and THF (5 mL) was treated with diisopropylethylamine (0.27 mL, 1.50 mmol). The mixture was cooled to 0° C., and then isopropyl chloroformate (1.0M in toluene, 0.82 mL, 0.82 mmol) was added dropwise. The reaction mixture was allowed to warm to ambient temperature and stirred overnight, diluted with CH2Cl2 (100 mL) and washed with water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a light brown oil. The crude material was purified by flash chromatography on a silica gel column eluted with 1:5 acetone/CH2Cl2 to give 0.31 g (93%) of the title compound as a white foam. 1H NMR (400 MHz, CDCl3): δ 8.38 (d, 1H, J=2.9 Hz), 8.13 (d, 2H, J=8.5 Hz), 8.01 (d, 2H, J=8.5 Hz), 7.73 (d, 1H, J=8.8 Hz), 7.35-7.25 (m, 1H), 4.91 (septet, 1H, J=6.2 Hz), 4.35-4.15 (m, 3H), 3.08 (s, 3H), 2.80-2.65 (m, 2H), 1.95-1.65 (m, 3H), 1.45-1.25 (m, 5H), 1.23 (d, 6H, J=6.3 Hz); LRMS (ESI), m/z 447 (M+H).

Workup

  1. temperatureto warm to ambient temperature
  2. washwashed with water, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated to a light brown oil
  6. customThe crude material was purified by flash chromatography on a silica gel column
  7. washeluted with 1:5 acetone/CH2Cl2

Sources & evidence

ORD record
ord-ee13e6bfc21b430189ca67aa03f24e2c
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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