1,2-Dichloroethane → {(1S,2S,5R)-3-[(2-methyl-5-phenyl-1,3-thiazol-4-yl)carbonyl]-3-azabicyclo[3.1.0]hex-2-yl}methanol

HRID 1662094Notes

Reaction equation

HRID 1662094 reaction equation
[Si]([O:8][CH2:9][C@H:10]1[N:15]([C:16]([O:18]C(C)(C)C)=O)[CH2:14][C@H:13]2[C@@H:11]1[CH2:12]2)(C(C)(C)C)(C)C.Cl.[CH3:24][C:25]1[S:26][C:27]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[C:28](C(O)=O)[N:29]=1.C(N(CC)CC)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>O1CCOCC1.C(Cl)Cl>[CH3:24][C:25]1[S:26][C:27]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[C:28]([C:16]([N:15]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:9][OH:8])=[O:18])[N:29]=1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 9435352-methyl-5-phenyl-1,3-thiazole-4-carboxylic AcidHCID 59369795tert-butyl (1S,2S,5R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate

Product 1

HCID 59369815{(1S,2S,5R)-3-[(2-methyl-5-phenyl-1,3-thiazol-4-yl)carbonyl]-3-azabicyclo[3.1.0]hex-2-yl}methanol

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 4-4 (0.175 g, 0.534 mmol) in dioxane (1.4 mL) at 25° C. was added a solution of HCl in dioxane (1.33 mL, 5.34 mmol, 4M in dioxane) and the reaction mixture was stirred 2 h. The reaction concentrated directly to afford a white solid. The white solid was resuspended in CH2Cl2 (1.4 mL) at ambient temperature and to the mixture was added 1-2 (0.141 g, 0.641 mmol), triethylamine (0.27 g, 2.7 mmol), EDC (0.154 g, 0.801 mmol) and HOBT (0.123 g, 0.801 mmol). The reaction was stirred 15 h and quenched with saturated NaHCO3 (5 mL). The reaction mixture was diluted with EtOAc (20 mL) and washed with saturated NaHCO3 (3×15 mL). The combined organic phase was dried over magnesium sulfate and concentrated. The residue was purified by normal phase silica gel chromatography (0 to 100% EtOAc in hexanes, then 0 to 25% MeOH in EtOAc) to afford the product (4-5) as a foamy solid. ESI+ MS: [M+H]+ 315.2.

Workup

  1. concentrationThe reaction concentrated directly
  2. customto afford a white solid
  3. stirringThe reaction was stirred 15 h
  4. customquenched with saturated NaHCO3 (5 mL)
  5. additionThe reaction mixture was diluted with EtOAc (20 mL)
  6. washwashed with saturated NaHCO3 (3×15 mL)
  7. dry with materialThe combined organic phase was dried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by normal phase silica gel chromatography (0 to 100% EtOAc in hexanes

Sources & evidence

ORD record
ord-e354d4198a4b44069d15cfd954c71c05
Source dataset
uspto-grants-2011_10
Patent number
US08030495B2

Reaction notes

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