Pyridine → 4-Chlorobutyl (1S,2E)-3-{(1R,2R,3S,5R)-2-[(2Z)-7-(Ethylamino)-7-oxohept-2-en-1-yl]-3,5-dihydroxycyclopentyl}-1-(2-phenylethyl)prop-2-en-1-yl Carbonate

HRID 422893Notes

Reaction equation

HRID 422893 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].B([O-])[O-].N1C=CC=CC=1.Cl[C:41]([O:43][CH2:44][CH2:45][CH2:46][CH2:47][Cl:48])=[O:42]>C1COCC1.CN(C1C=CN=CC=1)C>[C:41](=[O:42])([O:28][C@@H:19]([CH2:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)/[CH:18]=[CH:17]/[C@H:16]1[C@H:15]([OH:29])[CH2:14][C@H:13]([OH:30])[C@@H:12]1[CH2:11]/[CH:10]=[CH:9]\[CH2:8][CH2:7][CH2:6][C:4]([NH:3][CH2:2][CH3:1])=[O:5])[O:43][CH2:44][CH2:45][CH2:46][CH2:47][Cl:48]

Participants

6

Reactant 3

HCID 1049Pyridine2×HCID 27333284-Chlorobutyl carbonochloridate2×HCID 178465099HCID 178465099, compound

Product 1

HCID 582316334-Chlorobutyl (1S,2E)-3-{(1R,2R,3S,5R)-2-[(2Z)-7-(Ethylamino)-7-oxohept-2-en-1-yl]-3,5-dihydroxycyclopentyl}-1-(2-phenylethyl)prop-2-en-1-yl CarbonateYield 134%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of bimatoprost boronate b-1 (529 mg, 1.10 mmol) in THF was added DMAP (6.9 mg, 0.055 mmol). The solution was cooled to 0° C. and successively slowly added pyridine (0.22 mL, 2.75 mmol) and 4-chlorobutyl chloroformate (0.375 mL, 2.75 mmol). Allowed to stir at ambient temperature over 2 days. Added more pyridine (89 uL, 1.11 mmol) and 4-chlorobutyl chloroformate (150 uL, 1.10 mmol) and stirred for another 24 h. The resultant mixture was concentrated under reduced pressure, residue partitioned with ethyl acetate and water. Washed organic layer with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to provide 808 mg (134%) of a crude oil, which was used without further purification.

Workup

  1. stirringstirred for another 24 h
  2. concentrationThe resultant mixture was concentrated under reduced pressure, residue
  3. custompartitioned with ethyl acetate and water
  4. dry with materialWashed organic layer with brine, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-140901632d314fde8f47f5142f679081
Source dataset
uspto-grants-2012_01
Patent number
US08101658B2

Reaction notes

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