Sodium borohydride → 5-(benzyloxy)-8-({benzyl[6-(4-phenylbutoxy)hexyl]amino}acetyl)-2H-1,4-benzoxazin-3(4H)-one

HRID 749236Notes

Reaction equation

HRID 749236 reaction equation
[CH2:1]([O:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([C:20](=[O:24])[CH:21](O)O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:25]([NH:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][CH2:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[BH4-].[Na+]>C(Cl)Cl.CO.C(O)(=O)C>[CH2:1]([O:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([CH:20]([OH:24])[CH2:21][N:32]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][CH2:42][CH2:43][C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:1]([O:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([C:20](=[O:24])[CH2:21][N:32]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][CH2:42][CH2:43][C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 4311764Sodium borohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 10914757N-benzyl-6-(4-phenylbutoxy)hexan-1-amineHCID 231061485-(benzyloxy)-8-(dihydroxyacetyl)-2H-1,4-benzoxazin-3(4H)-one

Product 2

HCID 693159345-(Benzyloxy)-8-(2-{benzyl[6-(4-phenylbutoxy)hexyl]amino}-1-hydroxyethyl)-2H-1,4-benzoxazin-3(4H)-oneHCID 693175385-(benzyloxy)-8-({benzyl[6-(4-phenylbutoxy)hexyl]amino}acetyl)-2H-1,4-benzoxazin-3(4H)-oneYield 56.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 5-(benzyloxy)-8-(dihydroxyacetyl)-2H-1,4-benzoxazin-3(4H)-one (DE 3134590 A1) (150 mg) in dry DCM (2 ml) was treated with acetic acid and N-benzyl-6-(4-phenylbutoxy)hexan-1-amine (320 mg) (Tetrahedron Letters. 1994, 35, 9375) and stirred for 4 hr. Sodium triacetoxyborohydride (216 mg) was added and the reaction mixture stirred at room temperature for 3 days. Sodium borohydride (35 mg) in methanol (2 ml) was added and stirring continued for a further 2 h. The reaction mixture was quenched with water and partitioned between water and DCM. The organic phase was dried and concentrated in vacuo. The residue was purified by chromatography (Hexane-EtOAc, SPE) to give the title compound as a mixture with 5-(benzyloxy)-8-({benzyl[6-(4-phenylbutoxy)hexyl]amino}acetyl)-2H-1,4-benzoxazin-3(4H)-one (81.6 mg).

Workup

  1. stirringthe reaction mixture stirred at room temperature for 3 days
  2. stirringstirring
  3. waitcontinued for a further 2 h
  4. customThe reaction mixture was quenched with water
  5. custompartitioned between water and DCM
  6. customThe organic phase was dried
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography (Hexane-EtOAc, SPE)

Sources & evidence

ORD record
ord-51a85d211ac34e3da3865362d14542e6
Source dataset
uspto-grants-2008_07
Patent number
US07402598B2

Reaction notes

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