Acetyl chloride → HCID 86676610, compound

HRID 85667Notes

Reaction equation

HRID 85667 reaction equation
[O:1]=[S:2]1(=[O:51])[CH2:7][CH2:6][N:5]([CH2:8][C:9]([NH:11][C@:12]23[CH2:47][CH2:46][C@@H:45]([C:48]([CH3:50])=[CH2:49])[C@@H:13]2[C@@H:14]2[C@@:27]([CH3:30])([CH2:28][CH2:29]3)[C@@:26]3([CH3:31])[C@@H:17]([C@:18]4([CH3:44])[C@@H:23]([CH2:24][CH2:25]3)[C:22]([CH3:33])([CH3:32])[C:21]([C:34]3[CH:43]=[CH:42][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:36][CH:35]=3)=[CH:20][CH2:19]4)[CH2:16][CH2:15]2)=O)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.[C:61](Cl)(=[O:63])[CH3:62]>ClC(Cl)C>[C:61]([N:11]([CH2:9][CH2:8][N:5]1[CH2:4][CH2:3][S:2](=[O:51])(=[O:1])[CH2:7][CH2:6]1)[C@:12]12[CH2:47][CH2:46][C@@H:45]([C:48]([CH3:50])=[CH2:49])[C@@H:13]1[C@@H:14]1[C@@:27]([CH3:30])([CH2:28][CH2:29]2)[C@@:26]2([CH3:31])[C@@H:17]([C@:18]3([CH3:44])[C@@H:23]([CH2:24][CH2:25]2)[C:22]([CH3:33])([CH3:32])[C:21]([C:34]2[CH:35]=[CH:36][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:42][CH:43]=2)=[CH:20][CH2:19]3)[CH2:16][CH2:15]1)(=[O:63])[CH3:62]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 86676611HCID 86676611, compound

Product 1

HCID 86676610HCID 86676610, compoundYield 76.1%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((1,1-dioxido-4-thiomorpholinyl)acetyl)amino)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-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 (0.05 g, 0.071 mmol) in dichloroethane (1 mL) and Hunig's base (0.062 mL, 0.355 mmol) was added acetyl chloride (0.020 mL, 0.284 mmol). The mixture was heated to 50° C. After heating the mixture for 71.25 h, the mixture was cooled to rt and was directly loaded onto a 12 g Thomson silica gel column and was purified by Biotage flash chromatography using a 0-5% MeOH in dichloromethane gradient. The fractions containing the expected product were combined and were concentrated under reduced pressure to give methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(acetyl(2-(1,1-dioxido-4-thiomorpholinyl)ethyl)amino)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-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 (40 mg, 0.054 mmol, 75%) as a clear, colorless film. LCMS: m/e 747.5 (M+H)+, 2.26 min (method 2).

Workup

  1. temperatureAfter heating the mixture for 71.25 h
  2. temperaturethe mixture was cooled to rt
  3. customwas purified by Biotage flash chromatography
  4. additionThe fractions containing the expected product
  5. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-170464467f6b427ca1e3ba3553e26adc
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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