Cyclopropanecarbonyl chloride → HCID 90281581, compound

HRID 2205277Notes

Reaction equation

HRID 2205277 reaction equation
[CH3:1][O:2][C:3](=[O:29])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH2:8][CH:9]1[CH2:18][CH:17]([OH:19])[CH:16]([CH2:20][CH2:21][CH:22]([OH:28])[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH:10]1[CH2:11]2.CCN(C(C)C)C(C)C.[CH:39]1([C:42](Cl)=[O:43])[CH2:41][CH2:40]1>CN(C1C=CN=CC=1)C.C(Cl)Cl.CC(OC)(C)C>[OH:28][CH:22]([CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:21][CH2:20][CH:16]1[CH:10]2[CH2:11][C:12]3[C:7]([CH2:8][CH:9]2[CH2:18][CH:17]1[O:19][C:42]([CH:39]1[CH2:41][CH2:40]1)=[O:43])=[C:6]([O:5][CH2:4][C:3]([O:2][CH3:1])=[O:29])[CH:15]=[CH:14][CH:13]=3

Participants

7

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 59733188HCID 59733188, compound

Product 1

HCID 90281581HCID 90281581, compoundYield 112.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A solution of [2-Hydroxy-1-(3-hydroxy-octyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-yloxy]-acetic acid methyl ester (32 mg, 0.06 mmol), DIPEA (31 μl, 0.18 mmol) and DMAP (1 crystal) in DCM (2 ml) was treated with cyclopropanecarbonyl chloride (8 μl, 0.08 mmol) and stirred for 24 hr at RT under nitrogen. The reaction mixture was diluted with MTBE and washed with saturated sodium bicarbonate solution and brine, dried over sodium sulfate and concentrated under vacuum. The residue was purified by silica gel chromatography. This resulting material was dissolved in MeOH/THE (4 ml), treated with Amberlite IR120H and stirred 24 hr. The reaction mixture was filtered and concentrated to yield cyclopropanecarboxylic acid 1-(3-hydroxy-octyl)-5-methoxycarbonylmethoxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-yl ester (32 mg) as an oil. 1HNMR: (400 MHz, DMSO-d6) δ 7.06 (d, 1H, J=7.6); 6.80 (d, 1H, J=7.2); 6.63 (d, 1H, J=8.8); 4.78 (s, 2H); 4.1-4.2 (m, 1H); 4.05-4.50 (m, 1H); 3.68 (s, 3H); 2.6-2.8 (m, 2H); 2.4-2.5 (m, 2H); 2.20-2.35 (m, 1H); 2.10-2.20 (m, 1H); 1.8-1.95 (m, 1H); 1.10-1.16 (m, 15H); 0.95-1.10 (m, 1H); 0.70-0.90 (m, 7H); MS: m/z 495 [M+Na]+

Workup

  1. washwashed with saturated sodium bicarbonate solution and brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by silica gel chromatography
  5. dissolutionThis resulting material was dissolved in MeOH/THE (4 ml)
  6. additiontreated with Amberlite IR120H
  7. stirringstirred 24 hr
  8. filtrationThe reaction mixture was filtered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-b407d8930dec4d58a3db79213c29f083
Source dataset
uspto-grants-2016_06
Patent number
US09371264B2

Reaction notes

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