Lithium hydroxide, monohydrate → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-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)benzoic acid

HRID 85609Notes

Reaction equation

HRID 85609 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:12]([NH:14][C@:15]23[CH2:50][CH2:49][C@@H:48]([C:51]([CH3:53])=[CH2:52])[C@@H:16]2[C@@H:17]2[C@@:30]([CH3:33])([CH2:31][CH2:32]3)[C@@:29]3([CH3:34])[C@@H:20]([C@:21]4([CH3:47])[C@@H:26]([CH2:27][CH2:28]3)[C:25]([CH3:36])([CH3:35])[C:24]([C:37]3[CH:46]=[CH:45][C:40]([C:41]([O:43]C)=[O:42])=[CH:39][CH:38]=3)=[CH:23][CH2:22]4)[CH2:19][CH2:18]2)=[O:13])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][C:9]1([C:12]([NH:14][C@:15]23[CH2:50][CH2:49][C@@H:48]([C:51]([CH3:53])=[CH2:52])[C@@H:16]2[C@@H:17]2[C@@:30]([CH3:33])([CH2:31][CH2:32]3)[C@@:29]3([CH3:34])[C@@H:20]([C@:21]4([CH3:47])[C@@H:26]([CH2:27][CH2:28]3)[C:25]([CH3:36])([CH3:35])[C:24]([C:37]3[CH:46]=[CH:45][C:40]([C:41]([OH:43])=[O:42])=[CH:39][CH:38]=3)=[CH:23][CH2:22]4)[CH2:19][CH2:18]2)=[O:13])[CH2:11][CH2:10]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68357872methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-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)benzoate

Product 1

HCID 683580634-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-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)benzoic acidYield 38.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-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)benzoate (101 mg, 0.139 mmol) in THF (5 mL) was added a solution of lithium hydroxide monohydrate (17.49 mg, 0.417 mmol) in water (1.000 mL). The resulting mixture was stirred at 75° C. After 18 h, the reaction mixture was concentrated. The residue was redissolved in THF/MeOH, silica gel (2 g) was added and the mixture was concentrated to dryness. The absorbed material was loaded onto a silica gel column (25 g cartridge) and eluted with 0% B (solvent B=(90:10 DCM:MeOH, A=100% DCM) to 50% B for 180 mL, then hold at 50% B for 900 mL. Thus was obtained 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(1-(tert-butoxycarbonylamino)cyclopropanecarboxamido)-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)benzoic acid (39 mg, 0.054 mmol, 38.6% yield) as white solid. LCMS: m/e 713.6 (M+H)+, 2.32 min (method 1). 1H NMR (500 MHz, 1:1 CDCl3:METHANOL-d4) δ 7.92 (d, J=8.2 Hz, 2H), 7.20 (d, J=8.2 Hz, 3H), 6.62 (br. s., 1H), 5.33-5.24 (m, 1H), 4.72 (s, 1H), 4.63 (s, 1H), 2.61-2.36 (m, 3H), 2.13 (dd, J=17.2, 6.3 Hz, 1H), 2.04-1.95 (m, 1H), 1.73 (br. s., 1H), 1.71 (s, 3H), 1.41 (d, J=6.1 Hz, 2H), 1.26 (br. s., 9H), 1.15 (s, 3H), 1.10 (br. s., 1H), 1.03 (s, 3H), 1.02 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H), 0.88 (d, J=6.7 Hz, 2H), 0.86-0.83 (m, 2H).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. dissolutionThe residue was redissolved in THF/MeOH
  3. additionsilica gel (2 g) was added
  4. concentrationthe mixture was concentrated to dryness
  5. washeluted with 0% B (solvent B=(90:10 DCM

Sources & evidence

ORD record
ord-bfe36d09fd54421291e6703a33a9eb1d
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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