Hydrochloric Acid → Thioacetic acid S-[(E)-4-((3S,7R,10R,13R,14S)-14-hydroxy-7,13-diisopropyl-10-methyl-5,8,11,16-tetraoxo-1,2-dioxa-6,9,12-triaza-cyclohexadec-3-yl)-but-3-enyl]ester

HRID 539140Notes

Reaction equation

HRID 539140 reaction equation
[OH:1][C@H:2]1[CH2:17][C:16](=[O:18])[O:15][O:14][C@H:13](/[CH:19]=[CH:20]/[CH2:21][CH2:22][SH:23])[CH2:12][C:11](=[O:24])[NH:10][C@H:9]([CH:25]([CH3:27])[CH3:26])[C:8](=[O:28])[NH:7][C@H:6]([CH3:29])[C:5](=[O:30])[NH:4][C@@H:3]1[CH:31]([CH3:33])[CH3:32].C(N(C(C)C)CC)(C)C.[C:43](Cl)(=[O:45])[CH3:44].Cl>C(Cl)Cl.CCOC(C)=O>[OH:1][C@H:2]1[CH2:17][C:16](=[O:18])[O:15][O:14][C@H:13](/[CH:19]=[CH:20]/[CH2:21][CH2:22][S:23][C:43](=[O:45])[CH3:44])[CH2:12][C:11](=[O:24])[NH:10][C@H:9]([CH:25]([CH3:27])[CH3:26])[C:8](=[O:28])[NH:7][C@H:6]([CH3:29])[C:5](=[O:30])[NH:4][C@@H:3]1[CH:31]([CH3:33])[CH3:32]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 25152743HCID 25152743, compound

Product 1

HCID 25152962Thioacetic acid S-[(E)-4-((3S,7R,10R,13R,14S)-14-hydroxy-7,13-diisopropyl-10-methyl-5,8,11,16-tetraoxo-1,2-dioxa-6,9,12-triaza-cyclohexadec-3-yl)-but-3-enyl]esterYield 41%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 9 (24.7 mg, 0.035 mmol) in CH2Cl2 (1.4 mL) was added triethylsilane (28 μL, 0.175 mmol) followed by the dropwise addition of TFA (0.35 mL, 25% v/v). After stirring for 1 h the reaction mixture was concentrated in vacuo and put under high vacuum for 2 h to give the crude thiol 10. At 0° C. to a solution of thiol 10 in CH2Cl2 (0.45 mL) was added diisopropylethylamine (30 μL, 0.172 mmol) followed by acetyl chloride (2.43 μL, 0.034 mmol) in CH2Cl2 (0.1 mL). After stirring for 2 h 10 min 1M HCl (1 mL) was added followed by EtOAc (10 mL) the layers were separated and the organic layer was washed with sat. brine (10 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Purification by flash column chromatography (eluent 1:0-98:2-96:4-94:6-92.8 CH2Cl2/MeOH) gave the product 11 (7.3 mg, 0.014 mmol, 41%) as a white solid: Rf 0.47 MeOH/CH2Cl2 (1:9).

Workup

  1. additionwas added
  2. customwere separated
  3. washthe organic layer was washed with sat. brine (10 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customPurification by flash column chromatography (eluent 1:0-98:2-96:4-94:6-92.8 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-f73769d8cf8f415c8adc978c2dae6539
Source dataset
uspto-grants-2014_10
Patent number
US08865655B2

Reaction notes

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