Hydrochloric Acid → N-{(1R,3S)-5-Isopropoxy-6-methyl-3-[1-(2-phenyl-butyryl)-piperidin-4-yl]-isochroman-1-ylmethyl}formamide

HRID 2074428Notes

Reaction equation

HRID 2074428 reaction equation
[CH:1]([O:4][C:5]1[C:14]([CH3:15])=[CH:13][CH:12]=[C:11]2[C:6]=1[CH2:7][C@@H:8]([CH:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)[O:9][C@H:10]2[CH2:16][NH:17][CH:18]=[O:19])([CH3:3])[CH3:2].[C:26]1([CH:32]([CH2:36][CH3:37])[C:33](Cl)=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(N(CC)CC)C.Cl>ClCCl>[CH:1]([O:4][C:5]1[C:14]([CH3:15])=[CH:13][CH:12]=[C:11]2[C:6]=1[CH2:7][C@@H:8]([CH:20]1[CH2:21][CH2:22][N:23]([C:33](=[O:34])[CH:32]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:36][CH3:37])[CH2:24][CH2:25]1)[O:9][C@H:10]2[CH2:16][NH:17][CH:18]=[O:19])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 981732-Phenylbutyryl chlorideHCID 11638795N-((1R,3S)-5-Isopropoxy-6-methyl-3-(4-piperidinyl)-1-isochromanylmethyl)formamide

Product 1

HCID 86612296N-{(1R,3S)-5-Isopropoxy-6-methyl-3-[1-(2-phenyl-butyryl)-piperidin-4-yl]-isochroman-1-ylmethyl}formamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
10 °C

Procedure

Stir a solution of N-((1R,3S)-5-isopropoxy-6-methyl-3-(4-piperidinyl)-1-isochromanyl-methyl)formamide (200 mg, 0.58 mmole) in dichloromethane (3 mL), cool to 10° C. and add 2-phenylbutyryl chloride (115 mg, 0.64 mmole) and triethylamine (88 mg, 0.87 mmole). Allow to warm to room temperature and pour into dilute HCl. Separate the layers an extract the aqueous layer two times with 4 mL of dichloromethane. Wash the combined organic extracts with water and dry over Na2SO4. Purify the crude product on a 10 g silica gel column (eluting with ethyl acetate:heptane 3:1). Collect the appropriate fractions and concentrate to obtain the title compound. It was used without further purification in the next step.

Workup

  1. temperatureAllow to warm to room temperature
  2. customSeparate the layers
  3. extractionan extract the aqueous layer two times with 4 mL of dichloromethane
  4. washWash the combined organic extracts with water
  5. dry with materialdry over Na2SO4
  6. customPurify the crude product
  7. washon a 10 g silica gel column (eluting with ethyl acetate:heptane 3:1)
  8. customCollect the appropriate fractions
  9. concentrationconcentrate

Sources & evidence

ORD record
ord-4fe8714f75574e5e85ca38b454af9db3
Source dataset
uspto-grants-2011_04
Patent number
US07919508B2

Reaction notes

Loading…