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

HRID 516954Notes

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

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, 1H), 1.00-0.88 (m, 3H).

Workup

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

Sources & evidence

ORD record: ord-7ea4aea808a441a0939223cf0869ecc4
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115054B2

Reaction notes

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