Lithium Hydroxide → (S)-4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13 aR,13bR)-3 a-((2-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylic acid

HRID 338665Notes

Reaction equation

HRID 338665 reaction equation
[C@H:1]12[CH2:55][C@H:4]([N:5]([CH2:7][CH2:8][NH:9][C@:10]34[CH2:51][CH2:50][C@@H:49]([C:52]([CH3:54])=[CH2:53])[C@@H:11]3[C@@H:12]3[C@@:25]([CH3:28])([CH2:26][CH2:27]4)[C@@:24]4([CH3:29])[C@@H:15]([C@:16]5([CH3:48])[C@@H:21]([CH2:22][CH2:23]4)[C:20]([CH3:31])([CH3:30])[C:19]([C:32]4[CH2:37][CH2:36][C@H:35]([C:38]([O:40]CC6C=CC=CC=6)=[O:39])[CH2:34][CH:33]=4)=[CH:18][CH2:17]5)[CH2:14][CH2:13]3)[CH2:6]1)[CH2:3][O:2]2.[OH-].[Li+]>C1COCC1.CO>[C@H:1]12[CH2:55][C@H:4]([N:5]([CH2:7][CH2:8][NH:9][C@:10]34[CH2:51][CH2:50][C@@H:49]([C:52]([CH3:54])=[CH2:53])[C@@H:11]3[C@@H:12]3[C@@:25]([CH3:28])([CH2:26][CH2:27]4)[C@@:24]4([CH3:29])[C@@H:15]([C@:16]5([CH3:48])[C@@H:21]([CH2:22][CH2:23]4)[C:20]([CH3:31])([CH3:30])[C:19]([C:32]4[CH2:37][CH2:36][C@H:35]([C:38]([OH:40])=[O:39])[CH2:34][CH:33]=4)=[CH:18][CH2:17]5)[CH2:14][CH2:13]3)[CH2:6]1)[CH2:3][O:2]2

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86701817(S)-benzyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylate

Product 1

HCID 72201483(S)-4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13 aR,13bR)-3 a-((2-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylic acidYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of (S)-benzyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylate in THF (1.5 mL) and MeOH (0.5 mL) was added 1N lithium hydroxide (0.115 mL, 0.115 mmol). The reaction was stirred at 75° C. After 3 h the reaction mixture was concentrated and the crude material was dissolved in THF (2 mL)/H2O (150 μL) and purified by reverse phase prep-HPLC using prep-HPLC method 15 and dried under vacuum to give (S)-4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13 aR,13bR)-3a-((2-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylic acid (21 mg, 0.023 mmol, 80% yield) as a white solid. LC/MS: m/e 659.5 (M+H)+, 34.14 min (method 8). 1H NMR (400 MHz, 1:1 CDCl3:METHANOL-d4) δ 5.33 (br. s., 1H), 5.17 (d, J=4.6 Hz, 1H), 4.78 (s, 1H), 4.70 (br. s., 1H), 4.52 (s, 1H), 4.03 (d, J=8.6 Hz, 1H), 3.75 (br. s., 1H), 3.72 (d, J=8.6 Hz, 1H), 3.18-3.09 (m, 2H), 3.09-2.92 (m, 4H), 2.79-2.64 (m, 2H), 2.53-2.42 (m, 1H), 2.31-2.23 (m, 2H), 2.16 (br. s., 2H), 2.04-1.93 (m, 8H), 1.81-1.73 (m, 2H), 1.72 (s, 3H), 1.69-1.63 (m, 1H), 1.61-1.33 (m, 12H), 1.30 (dd, J=12.2, 3.4 Hz, 1H), 1.24 (br. s., 1H), 1.20-1.14 (m, 1H), 1.12-1.09 (m, 3H), 1.05 (s, 3H), 0.97 (s, 3H), 0.90 (s, 3H), 0.88 (s, 3H)

Workup

  1. concentrationAfter 3 h the reaction mixture was concentrated
  2. dissolutionthe crude material was dissolved in THF (2 mL)/H2O (150 μL)
  3. custompurified by reverse phase prep-HPLC using prep-HPLC method 15
  4. customdried under vacuum

Sources & evidence

ORD record
ord-a35326e9ae474e7aa99682e07f442c03
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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