4-Chlorobutyl carbonochloridate → 4-Chlorobutyl (2R,3R)-3-[(2Z)-7-(Ethylamino)-7-oxohept-2-en-1-yl]-4-hydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl Carbonate

HRID 422890Notes

Reaction equation

HRID 422890 reaction equation
[CH3:1][CH2:2][NH:3][C:4]([CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][C@@H:12]1[C@@H:16](/[CH:17]=[CH:18]/[C@@H:19]([OH:28])[CH2:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@H:15]([OH:29])[CH2:14][C@@H:13]1[OH:30])=[O:5].Cl[C:32]([O:34][CH2:35][CH2:36][CH2:37][CH2:38][Cl:39])=[O:33]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:32](=[O:33])([O:29][CH:15]1[CH2:14][CH:13]([OH:30])[C@H:12]([CH2:11]/[CH:10]=[CH:9]\[CH2:8][CH2:7][CH2:6][C:4]([NH:3][CH2:2][CH3:1])=[O:5])[C@H:16]1/[CH:17]=[CH:18]/[C@@H:19]([OH:28])[CH2:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[O:34][CH2:35][CH2:36][CH2:37][CH2:38][Cl:39]

Participants

5

Reactant 2

HCID 27333284-Chlorobutyl carbonochloridateHCID 5311027Bimatoprost

Product 1

HCID 866526684-Chlorobutyl (2R,3R)-3-[(2Z)-7-(Ethylamino)-7-oxohept-2-en-1-yl]-4-hydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl Carbonate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of bimatoprost (Cayman Chemicals 16820, Lot 188757; 123 mg, 0.30 mmol) in DCM (3 mL) at 0° C. was added DMAP (39 mg, 0.31 mmol) followed by the slow addition of 4-chlorobutyl chloroformate (43 uL, 0.31 mmol). After 3 days at ambient temperature, the mixture was diluted with DCM and washed with water (1×) and brine (1×). The DCM layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude mixture of regioisomers and diacylated products was submitted to column chromatography (ethyl acetate-hexane 25-100%, followed by methanol-dichloromethane (5-15%) to provide as the major component isolated, 11-acylated chloride g-1 (25 mg, 15%) as a colorless oil.

Workup

  1. washwashed with water (1×) and brine (1×)
  2. dry with materialThe DCM layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. additionThe crude mixture of regioisomers and diacylated products
  5. customto provide as the major component
  6. customisolated

Sources & evidence

ORD record
ord-ade8fce79f28414fbf58cd652565d1f7
Source dataset
uspto-grants-2012_01
Patent number
US08101658B2

Reaction notes

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