Hydrochloric Acid → HCID 23253218, compound

HRID 724546Notes

Reaction equation

HRID 724546 reaction equation
[CH3:1][CH:2]([CH:9]1[C:13]2([CH3:30])[CH:14]([OH:29])[CH2:15][CH:16]3[C:21]4([CH3:27])[CH2:22][CH2:23][CH:24]([OH:26])[CH2:25][CH:20]4[CH2:19][CH:18]([OH:28])[CH:17]3[CH:12]2[CH2:11][CH2:10]1)[CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6].[C:31]1([CH3:41])[CH:36]=[CH:35][C:34]([S:37](Cl)(=[O:39])=[O:38])=[CH:33][CH:32]=1.CC(OC)(C)C.Cl>N1C=CC=CC=1.O>[CH3:8][O:7][C:5](=[O:6])[CH2:4][CH2:3][C@H:2]([C@@H:9]1[C@:13]2([CH3:30])[C@H:12]([C@H:17]3[C@H:16]([CH2:15][C@@H:14]2[OH:29])[C@:21]2([CH3:27])[C@@H:20]([CH2:25][C@H:24]([O:26][S:37]([C:34]4[CH:35]=[CH:36][C:31]([CH3:41])=[CH:32][CH:33]=4)(=[O:39])=[O:38])[CH2:23][CH2:22]2)[CH2:19][C@H:18]3[OH:28])[CH2:11][CH2:10]1)[CH3:1]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 15413tert-Butyl methyl etherHCID 277782methyl 4-(3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate

Product 1

HCID 23253218HCID 23253218, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent2×

Conditions

Temperature
-8 °C

Procedure

To a solution of cholic acid methyl ester (1000.0 g, 2.366 mol) in pyridine (2250 mL) at −10° C. was added a solution of p-toluenesulfonyl chloride (654.2 g, 2.431 mol) in pyridine (650 mL) dropwise over 2.5 hours while maintaining the reaction temperature at −10 to −6° C. The solution was mixed at −10° C. for an additional 12.5 hours, diluted with water (61.8 g) with continued cooling. The mixture at −7.5° C. was added over a period of 43 minutes to a mixture of MTBE (5 L) and 6N HCl (6.2 L). The layers were separated and the organic phase was washed with 7% NaHCO3 (2 L), followed by 2% NaCl (2 L), and finally with pH 7 phosphate buffer (2 L). The organic phase was filtered, concentrated under reduced pressure with MTBE (3×200 mL) to give 1608.93 g of a very viscous pale-straw colored oil (95.3% potency adjusted yield) that was used directly in the next step. 1H NMR (CDCl3, 400 MHz) δ 7.79 (d, J=8.5 Hz, 2 H), 7.32 (d, J=8.6 Hz, 2 H), 4.40–4.31 (m, 1 H), 3.97 (br s, 1 H), 3.83 (br s, 1 H), 3.68 (s, 3 H), 2.60–2.50 (m, 1 H), 2.45 (s, 3 H), 2.43–1.34 (m, 25 H), 0.99 (d, J=6.3 Hz, 3 H), 0.88 (s, 3 H), 0.69 (s, 3 H). MS (ESI) Expected=576; base=594.2 (576+NH4+).

Workup

  1. additionThe solution was mixed at −10° C. for an additional 12.5 hours
  2. customThe layers were separated
  3. washthe organic phase was washed with 7% NaHCO3 (2 L)
  4. filtrationThe organic phase was filtered
  5. concentrationconcentrated under reduced pressure with MTBE (3×200 mL)
  6. customto give
  7. custom1608.93 g of a very viscous pale-straw colored oil (95.3% potency adjusted yield) that

Sources & evidence

ORD record
ord-dfd5a2553dda4353952a6c18907bf7b3
Source dataset
uspto-grants-2006_11
Patent number
US07141559B2

Reaction notes

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