HCID 70448960, compound → HCID 13799250, compound

HRID 1905851Notes

Reaction equation

HRID 1905851 reaction equation
[OH:1][C@@H:2]1[CH2:25][CH2:24][C@@:23]2([CH3:26])[C@H:4]([CH2:5][C:6]([CH3:29])=[C:7]3[C@@H:22]2[CH2:21][C@H:20]([OH:27])[C@@:19]2([CH3:28])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:18])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH2:3]1>C(OCC)(=O)C>[OH:1][C@@H:2]1[CH2:25][CH2:24][C@@:23]2([CH3:26])[C@H:4]([CH:5]=[C:6]([CH3:29])[C@@H:7]3[C@@H:22]2[CH2:21][C@H:20]([OH:27])[C@@:19]2([CH3:28])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:18])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH2:3]1

Participants

3

Reactant 1

HCID 70448960HCID 70448960, compound

Product 1

HCID 13799250HCID 13799250, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2-(3α,7ξ,12α-Trihydroxy-7ξ-methyl-24-nor-5β-cholanyl)-4,4-dimethyl-2-oxazoline from Example 6 (2.5 g) was dissolved in a solution of concentrated HCl (2 ml) and methanol (200 ml). The solution was refluxed for 6 hours, diluted with water, and extracted with ethyl acetate. The extract was washed with water, dried, and evaporated to dryness to give methyl ester derivatives of three hydration products. The residue was combined with the unsaturated dihydroxy fraction obtained in Example 7, (total, 2.6 g) and placed on a column of silica gel (150 g) impregnated with 15 g of AgNO3. Elution with increasing proportions of acetone in chloroform yielded two major fractions. Fraction 1, eluted with 7% acetone in chloroform, gave 480 mg of an oily residue. Alkaline hydrolysis of the residue and recrystallizations from ethyl acetate yielded colorless prisms of 3α,12α-dihydroxy-7-methyl-5β-chol-7-en-24-oic acid. Melting point, 160°-163° C. PMR (δ ppm): 0.79 (3H, s, 18--CH3), 0.86 (3H, s, 19--CH3), 1.16 (3H, d, J=6 Hz, 21--CH3), 1.73 (3H, s, 7--CH3), 3.70 (1H, m, 3β--H), 4.13 (1H, m, 12β--H). Fraction 2, eluted with 10% acetone in chloroform, yielded, approximately, a 1:1 mixture of two unsaturated compounds (1.59 g) on AGNO3 -TLC, GLC and GLC-MS. These two compounds were separated on a column of silica gel (150 g) impregnated with 15 g AgNO3 using increasing concentrations of ethyl acetate in benzene. Elution with 35% ethyl acetate in benzene (Fraction 2A), followed by alkaline hydrolysis, afforded 640 mg of 3α,12α-dihydroxy-7-methyl-5β-chol-6-en-24-oic acid. Recrystallization from ethyl acetate gave colorless needles melting at 144°-148° C. PMR (δ ppm): 0.79 (3H, s, 18--CH3), 0.89 (3H, s, 19--CH3), 1.22 (3H, d, J=6 Hz, 21--CH3), 1.69 (3H, s, 7--CH3), 3.70 (1H, m, 3β--H), 4.13 (1H, m, 12β--H), 5.36 (1H, m, 6--H). Fraction 2B, eluted with 40% ethyl acetate in benzene, gave a second compound (450 mg) which, after alkaline hydrolysis, was recrystallized from ethyl acetate to give colorless needles of 3α,12α-dihydroxy-7-methylene-5β-cholan-24-oic acid, mp 199°-202° C. PMR (δ ppm): 0.79 (3H, s, 18--CH3), 1.05 (3H, s, 19--CH3), 1.20 (3H, d, J=6 Hz, 21--CH3), 3.75 (1H, m, 3β--H), 4.16 (1H, m, 12β--H), 4.61 and 4.74 (2H, m, C=CH2).

Workup

  1. customMelting point, 160°-163° C
  2. washFraction 2, eluted with 10% acetone in chloroform
  3. customyielded
  4. customThese two compounds were separated on a column of silica gel (150 g)
  5. temperatureincreasing concentrations of ethyl acetate in benzene
  6. washElution with 35% ethyl acetate in benzene (Fraction 2A)
  7. customfollowed by alkaline hydrolysis

Sources & evidence

ORD record
ord-d904f7aea93645a3a1d4d7354c319b18
Source dataset
uspto-grants-1987_03
Patent number
US04648995

Reaction notes

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