Sodium Hydroxide → ((1R,3S)-1-AMINO-3-((R)-6-HEXYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CYCLOPENTYL)METHANOL

HRID 2199481Notes

Reaction equation

HRID 2199481 reaction equation
[CH2:1]([C@@H:7]1[CH2:16][CH2:15][C:14]2[CH:13]=[C:12]([C@H:17]3[CH2:26][CH2:25][C@@:19]4([NH:23]C(=O)[O:21][CH2:20]4)[CH2:18]3)[CH:11]=[CH:10][C:9]=2[CH2:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[OH-].[Na+]>O1CCOCC1.C(OCC)(=O)C>[NH2:23][C@:19]1([CH2:20][OH:21])[CH2:25][CH2:26][C@H:17]([C:12]2[CH:11]=[CH:10][C:9]3[CH2:8][C@H:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:16][CH2:15][C:14]=3[CH:13]=2)[CH2:18]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86730050HCID 86730050, compound

Product 1

HCID 77050638((1R,3S)-1-AMINO-3-((R)-6-HEXYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CYCLOPENTYL)METHANOLYield 78.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (5R,7S)-7-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)-3-oxa-1-azaspiro[4.4]nonan-2-one (400 mg, 1.125 mmol) in dioxane (30 mL) was added aqueous NaOH (1N, 20 mL). The reaction mixture was heated at 100° C. for 3 days, cooled to room temperature, diluted with ethyl acetate and washed with water. The organic layer was dried with MgSO4, filtered and concentrated. The crude material was purified on a silica gel cartridge (24 g) using an 20% (2N NH3/MeOH) in DCM/DCM gradient (0-75% of 20% (2N NH3/MeOH) in DCM over 13 CV) to afford 290 mg of ((1R,3S)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol. HPLC retention time=10.09 min (Condition H); LC/MS M+1=330; 1H NMR (400 MHz, methanol-d4) δ 7.03-6.91 (m, 3H), 3.54-3.41 (m, 2H), 3.01 (tt, J=11.1, 7.2 Hz, 1H), 2.87-2.69 (m, 3H), 2.34 (dd, J=16.2, 10.5 Hz, 1H), 2.20 (dd, J=13.0, 7.5 Hz, 1H), 2.07-1.84 (m, 3H), 1.83-1.60 (m, 3H), 1.60-1.48 (m, 1H), 1.47-1.25 (m, 11H), 1.00-0.88 (m, 3H).

Workup

  1. temperaturecooled to room temperature
  2. washwashed with water
  3. dry with materialThe organic layer was dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified on a silica gel cartridge (24 g)

Sources & evidence

ORD record
ord-e61576bd7e574796950726ffff2affd6
Source dataset
uspto-grants-2016_06
Patent number
US09359286B2

Reaction notes

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