Acetic Acid → HCID 178453938, compound

HRID 868896Notes

Reaction equation

HRID 868896 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][CH:3]=1.CC(O)=O.[C:13]([O:17][C:18](=[O:28])[NH:19][CH:20]1[CH2:25][CH2:24][CH:23]([CH:26]=O)[CH2:22][CH2:21]1)([CH3:16])([CH3:15])[CH3:14].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CCOCC>[C:13]([O:17][C:18](=[O:28])[NH:19][C@H:20]1[CH2:21][CH2:22][C@H:23]([CH2:26][NH:8][C:5]2[CH:6]=[CH:7][C:2]([I:1])=[CH:3][CH:4]=2)[CH2:24][CH2:25]1)([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 108934-IodoanilineHCID 5049666Sodium triacetoxyborohydrideHCID 11020615rac-tert-butyl N-[(1r,4r)-4-formylcyclohexyl]carbamate

Product 1

HCID 178453938HCID 178453938, compoundYield 79.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-iodo-phenylamine (1 g, 4.57 mmol) in DCM (25 ml) were successively added AcOH (0.523 ml, 9.13 mmol), (4-formyl-cyclohexyl)-carbamic acid tert-butyl ester (1.14 g, 5.02 mmol) and NaBH(OAc)3 (1.94 g, 9.13 mmol) at RT. The reaction mixture was stirred at RT for 1 h then diluted with Et2O and washed successively with a 2M aqueous HCl solution and a 2M aqueous Na2CO3 solution. The organic phase was dried over Na2SO4, filtered and evaporated to dryness. The resulting crude material was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, heptane/AcOEt 95:5→1:1) to yield the title compound (1.56 g, 3.62 mmol, 79%) as a colorless solid. TLC: RF=0.72 (heptane/AcOEt 1:1); HPLC: AtRet=2.64 min; LC-MS: m/z 431.4 [M+H]+; 1H NMR (400 MHz, DMSO-d6): 0.87-1.03 (m, 2H), 1.03-1.17 (m, 2H), 1.32-1.48 (m, 1H), 1.37 (s, 9H), 1.70-1.86 (m, 4H), 2.76-2.86 (m, 2H), 3.08-3.25 (m, 1H), 5.77-5.89 (m, 1H), 6.34-6.46 (m, 2H), 6.59-6.71 (m, 1H), 7.24-7.35 (m, 2H).

Workup

  1. customat RT
  2. washwashed successively with a 2M aqueous HCl solution
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe resulting crude material was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, heptane/AcOEt 95:5→1:1)

Sources & evidence

ORD record
ord-72ccfe7441684eb19df036b3abc4f61e
Source dataset
uspto-grants-2015_03
Patent number
US08969351B2

Reaction notes

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