Hydrochloric Acid → HCID 11070421, compound

HRID 488767Notes

Reaction equation

HRID 488767 reaction equation
S(C)C.[OH:4][C:5]1[CH:14]=[C:13]2[C:8]([CH2:9][C@H:10]([C:15]([NH:17][C@H:18]([CH2:22][N:23]3[CH2:28][CH2:27][C@:26]([C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=4)([CH3:29])[C@@H:25]([CH3:37])[CH2:24]3)[CH:19]([CH3:21])[CH3:20])=O)[NH:11][CH2:12]2)=[CH:7][CH:6]=1.Cl.CCOCC>C1COCC1.CO>[OH:36][C:32]1[CH:31]=[C:30]([C@:26]2([CH3:29])[CH2:27][CH2:28][N:23]([CH2:22][C@@H:18]([NH:17][CH2:15][C@H:10]3[CH2:9][C:8]4[C:13](=[CH:14][C:5]([OH:4])=[CH:6][CH:7]=4)[CH2:12][NH:11]3)[CH:19]([CH3:21])[CH3:20])[CH2:24][C@@H:25]2[CH3:37])[CH:35]=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1068Dimethyl SulfideHCID 3283Diethyl EtherHCID 9956146JDTic

Product 1

HCID 11070421HCID 11070421, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

A solution of 2M BH3.SMe2 in THF (0.495 mL 0.99 mmol) was added drop-wise to a −20° C.-solution of 14 (46 mg, 0.099 mmol) in 5 mL of dry THF. The reaction refluxed overnight. It was again cooled to −20° C. and 0.647 mL of MeOH was added. Contents stirred at room temperature for one hour. At room temperature, 1M HCl in ether (0.142 mL, 0.142 mmol) was added, and stirred for 30 minutes. The solvent was then removed under reduced pressure. The oil was then dissolved in 3:1 CH2Cl2:THF. Then, enough sat'd NaHCO3 was added to increase the pH to 10. The organic layer was separated and set aside. The aqueous layer was extracted five times with 3:1 CH2Cl2:THF. The organic layer was dried over sodium sulfate, and the solvent was removed under reduced pressure, yielding a yellowish foam. The crude product (0.03 g) was purified by silica preparative thin layer chromatography using a solvent gradient, starting with 25% (CHCl3:MeOH:NH4OH, 80:18:2) in CHCl3 then 40%, and finally 65%. This afforded 0.006 g of (3R)-3-{[((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)amino]methyl}-1,2,3,4-tetrahydro-7-isoquinolinol (19). 1H-NMR (MeOH): 7.12(t, J=5.1 Hz, 1H), 6.90 (d, J=4.1 Hz, 1H), 6.8(d, J=3.9 Hz, 1H), 6.76 (d, J=1.1 Hz, 1h), 6.61 (dd, J=5.8,2.2 Hz, 2H), 6.48 (d, J=1.2 Hz, 1H), 2.88-2.43 (m, 16H), 2.4-1.8 (m, 2H), 1.67 (d, J=13 Hz, 1H), 1.34 (s, 3H), 1.01 (d, J=6.9 Hz, 3H), 0.95 (d, J=6.9 Hz, 3H), 0.81 (d, J=3.4 Hz, 3H). LRMS (ES) m/z 452.3 (M+H)+.

Workup

  1. temperatureThe reaction refluxed overnight
  2. stirringstirred for 30 minutes
  3. customThe solvent was then removed under reduced pressure
  4. dissolutionThe oil was then dissolved in 3:1 CH2Cl2
  5. additionThen, enough sat'd NaHCO3 was added
  6. temperatureto increase the pH to 10
  7. customThe organic layer was separated
  8. extractionThe aqueous layer was extracted five times with 3:1 CH2Cl2
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. customthe solvent was removed under reduced pressure
  11. customyielding a yellowish foam
  12. customThe crude product (0.03 g) was purified by silica preparative thin layer chromatography

Sources & evidence

ORD record
ord-4301806f30d54b6797f38722e985a4ba
Source dataset
uspto-grants-2005_12
Patent number
US06974824B2

Reaction notes

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