Acetic Acid → HCID 178454036, compound

HRID 1624269Notes

Reaction equation

HRID 1624269 reaction equation
C(O)(=O)C.[C:5]([O:9][C:10](=[O:19])[NH:11][CH:12]1[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]1)([CH3:8])([CH3:7])[CH3:6].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[N:34]1[C:43]2[C@@H:42]([NH2:44])[CH2:41][CH2:40][CH2:39][C:38]=2[CH:37]=[CH:36][CH:35]=1>O1CCCC1.C(Cl)Cl>[C:5]([O:9][C:10](=[O:19])[NH:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([NH:44][C@@H:42]2[C:43]3[N:34]=[CH:35][CH:36]=[CH:37][C:38]=3[CH2:39][CH2:40][CH2:41]2)[CH2:14][CH2:13]1)([CH3:8])([CH3:7])[CH3:6]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 1512535tert-butyl N-(4-oxocyclohexyl)carbamateHCID 5049666Sodium triacetoxyborohydrideHCID 12031071(8S)-5,6,7,8-Tetrahydroquinolin-8-amine

Product 1

HCID 178454036HCID 178454036, compoundYield 30.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Acetic acid (2.9 mL, 50.7 mmol), (4-oxo-cyclohexyl)-carbamic acid tert-butyl ester (4.32 g, 20.2 mmol) and sodium triacetoxyborohydride (7.56 g, 35.7 mmol) were added to a solution of (S)-5,6,7,8-tetrahydro-quinolin-8-ylamine (2.86 g, 19.3 mmol) in tetrahydrofuran (78 mL) and the mixture was stirred at 25° C. for 3.5 h. The mixture was diluted with methylene chloride (500 mL) and washed with saturated sodium bicarbonate (600 mL). The aqueous layer was extracted with methylene chloride (2×150 mL). The combine organic layers were dried (Na2SO4) and concentrated. The crude mixture of isomers was purified by column chromatography on silica gel with methanol/methylene chloride (4:96) to afford the trans-isomer [4-((S)-5,6,7,8-tetrahydro-quinolin-8-ylamino)-trans-cyclohexyl]-carbamic acid tert-butyl ester as a white solid (2.01 g, 30%). 1H NMR (CDCl3) δ 1.06-1.39 (m, 4H), 1.69 (s, 9H), 1.65-1.80 (m, 2H), 1.90-2.14 (m, 5H), 2.16-2.25 (m, 1H), 2.29 (bs, 1H), 2.56-2.71 (m, 1H), 2.72-2.88 (m, 2H), 3.43 (bs, 1H), 3.92 (t, 1H, J=6.3 Hz), 4.39 (bs, 1H), 7.04 (dd, 1H, J=7.9, 4.5 Hz), 7.35 (d, 1H, J=7.5 Hz), 8.38 (d, 1H, J=4.5 Hz).

Workup

  1. washwashed with saturated sodium bicarbonate (600 mL)
  2. extractionThe aqueous layer was extracted with methylene chloride (2×150 mL)
  3. dry with materialThe combine organic layers were dried (Na2SO4)
  4. concentrationconcentrated
  5. additionThe crude mixture of isomers
  6. customwas purified by column chromatography on silica gel with methanol/methylene chloride (4:96)

Sources & evidence

ORD record
ord-4387122ef0b3490db926860f296639cf
Source dataset
uspto-grants-2014_07
Patent number
US08778967B2

Reaction notes

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