Water → HCID 178496602, compound

HRID 1190003Notes

Reaction equation

HRID 1190003 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:28]2[CH:33]([F:34])[CH2:32][CH2:31][CH2:30][C:29]=2[F:35])=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:25][CH2:24][C@H:23]([O:26][CH3:27])[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].C[O:37][C:38]([C:40]1[S:41][C:42]([C:63]2[CH2:68][CH2:67][CH2:66][CH:65]([F:69])[C:64]=2[F:70])=[CH:43][C:44]=1[N:45]([C@H:55]1[CH2:60][CH2:59][C@H:58]([O:61][CH3:62])[CH2:57][CH2:56]1)[C:46]([C@H:48]1[CH2:53][CH2:52][C@H:51]([CH3:54])[CH2:50][CH2:49]1)=[O:47])=[O:39].[Li+].[OH-].O>C1COCC1.O.CO>[F:35][C:29]1[CH2:30][CH2:31][CH2:32][CH:33]([F:34])[C:28]=1[C:7]1[S:6][C:5]([C:3]([OH:4])=[O:2])=[C:9]([N:10]([C@H:20]2[CH2:21][CH2:22][C@H:23]([O:26][CH3:27])[CH2:24][CH2:25]2)[C:11]([C@H:13]2[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]2)=[O:12])[CH:8]=1.[F:70][C:64]1[CH:65]([F:69])[CH2:66][CH2:67][CH2:68][C:63]=1[C:42]1[S:41][C:40]([C:38]([OH:39])=[O:37])=[C:44]([N:45]([C@H:55]2[CH2:56][CH2:57][C@H:58]([O:61][CH3:62])[CH2:59][CH2:60]2)[C:46]([C@H:48]2[CH2:53][CH2:52][C@H:51]([CH3:54])[CH2:50][CH2:49]2)=[O:47])[CH:43]=1

Participants

7

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 178499307HCID 178499307, compoundHCID 178499308HCID 178499308, compound

Product 2

HCID 178496602HCID 178496602, compoundHCID 178496603HCID 178496603, compound

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 5-(2,6-difluoro-cyclohex-1-enyl)-3-[(trans-4-methoxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester and 5-(2,3-Difluoro-cyclohex-1-enyl)-3-[(trans-4-methoxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (83 mg, 0.16 mmol) in THF: H2O: MeOH (3:1:2) (2 mL), was added LiOH in water (1N) (0.5 mL, 0.5 mmol). The reaction mixture was stirred at 70° C. for 5 h. The mixture was concentrated under reduced pressure on a rotary evaporator and the residue was treated with a solution of 0.1 N HCl and extracted in EtOAc. The EtOAc layer was dried over Na2SO4. Filtration and removal of the solvent under reduced pressure on a rotary evaporator followed by HPLC purification afforded 5-(2,6-difluoro-cyclohex-1-enyl)-3-[(trans-4-methoxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (3 mg) and 5-(2,3-difluoro-cyclohex-1-enyl)-3-[(trans-4-methoxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (3 mg) in overall 8% isolated yield.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure on a rotary evaporator
  2. additionthe residue was treated with a solution of 0.1 N HCl
  3. extractionextracted in EtOAc
  4. dry with materialThe EtOAc layer was dried over Na2SO4
  5. filtrationFiltration and removal of the solvent under reduced pressure
  6. customon a rotary evaporator
  7. customfollowed by HPLC purification

Sources & evidence

ORD record
ord-abdaedd4d8f64765bfb2b080ae31a71a
Source dataset
uspto-grants-2014_03
Patent number
US08674118B2

Reaction notes

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