Hydrochloric Acid → HCID 73776272, compound

HRID 530640Notes

Reaction equation

HRID 530640 reaction equation
[Cl:1]C1C=C(C2CN(C[C@H](O)C(F)(F)F)CCO2)C=C(Cl)C=1.ClC1C=CC(N=C=O)=CC=1.[Cl:32][C:33]1[CH:34]=[C:35]([C@H:40]2[O:45][CH2:44][CH2:43][N:42]([CH2:46][C@H:47]([O:52][C:53](=[O:62])[NH:54][C:55]3[CH:60]=[CH:59][C:58]([Cl:61])=[CH:57][CH:56]=3)[C:48]([F:51])([F:50])[F:49])[CH2:41]2)[CH:36]=[C:37]([Cl:39])[CH:38]=1.Cl>CCOCC.ClCCl>[ClH:1].[Cl:32][C:33]1[CH:34]=[C:35]([C@H:40]2[O:45][CH2:44][CH2:43][N:42]([CH2:46][C@H:47]([O:52][C:53](=[O:62])[NH:54][C:55]3[CH:60]=[CH:59][C:58]([Cl:61])=[CH:57][CH:56]=3)[C:48]([F:50])([F:51])[F:49])[CH2:41]2)[CH:36]=[C:37]([Cl:39])[CH:38]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 76934-Chlorophenyl IsocyanateHCID 73776273HCID 73776273, compoundHCID 118276748HCID 118276748, compound

Product 1

HCID 73776272HCID 73776272, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent

Procedure

In a 50 mL round-bottom flask, (2S)-3-(2-(3,5-dichlorophenyl)morpholino)-1,1,1-trifluoropropan-2-ol (665 mg, 1.93 mmol) was combined with dichloromethane (12 ml) to give a colorless solution. TEA (196 mg, 269 μl, 1.93 mmol) was added. 1-chloro-4-isocyanatobenzene (326 mg, 2.13 mmol) was added. The reaction mixture was stirred at room temperature overnight. Two major close-running spots of similar intensity could be seen by TLC (silica 10% EtOAc in hexanes eluent), a front-running spot and a later-running spot. The crude material was purified by flash chromatography (silica gel, 40 g, 5% to 20% EtOAc in hexanes gradient). The fractions that contained mostly front peak were pooled, concentrated and purified again by chromatography (silica, 40 g, 5-15% (3:1 dichloromethane:EtOAc) in hexane gradient) affording pure front peak product, assigned as (4-chloro-phenyl)-carbamic acid (S)-1-[(R)-2-(3,5-dichloro-phenyl)-morpholin-4-ylmethyl]-2,2,2-trifluoro-ethyl ester. This product was taken up in ether (30 mL) and treated with 1M HCl in ether (2.5 mL). Hexanes was added and the mixture was concentrated in vacuo to afford (4-chloro-phenyl)-carbamic acid (S)-1-[(R)-2-(3,5-dichloro-phenyl)-morpholin-4-ylmethyl]-2,2,2-trifluoro-ethyl ester hydrochloride (185 mg) as an off-white powder. (M+H)+=497, 499 m/e.

Workup

  1. customto give a colorless solution
  2. customTwo major close-running spots of similar intensity
  3. customThe crude material was purified by flash chromatography (silica gel, 40 g, 5% to 20% EtOAc in hexanes gradient)
  4. concentrationconcentrated
  5. custompurified again by chromatography (silica, 40 g, 5-15% (3:1 dichloromethane:EtOAc) in hexane gradient)
  6. customaffording pure front peak product
  7. concentrationthe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-0aee84dda9cf4ffc93c8fcc6f76cabe2
Source dataset
uspto-grants-2016_05
Patent number
US09353096B2

Reaction notes

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