4-Methylmorpholine → Methyl 4-[6-(cyclopentyloxycarbonyl) amino-2,3-dihydrobenz-1,4-oxazin-4-ylmethyl]-3-methoxybenzoate

HRID 1723211Notes

Reaction equation

HRID 1723211 reaction equation
Cl[C:2]([O:4][CH:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:3].[NH2:10][C:11]1[CH:12]=[CH:13][C:14]2[O:19][CH2:18][CH2:17][N:16]([CH2:20][C:21]3[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=3[O:31][CH3:32])[C:15]=2[CH:33]=1.CN1CCOCC1>ClCCl>[CH:5]1([O:4][C:2]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3[O:19][CH2:18][CH2:17][N:16]([CH2:20][C:21]4[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=4[O:31][CH3:32])[C:15]=3[CH:33]=2)=[O:3])[CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 2735892Cyclopentyl chloroformateHCID 14763126Methyl 4-(6-amino-2,3-dihydrobenz-1,4-oxazin4-ylmethyl)-3-methoxybenzoate

Product 1

HCID 14763127Methyl 4-[6-(cyclopentyloxycarbonyl) amino-2,3-dihydrobenz-1,4-oxazin-4-ylmethyl]-3-methoxybenzoateYield 52.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Cyclopentyl chloroformate (0.5 g.) was added in a single portion to a stirred solution of methyl 4-(6-amino-2,3-dihydrobenz-1,4-oxazin-4-ylmethyl)-3-methoxybenzoate (L) (1.0 g.) and N-methylmorpholine (0.314 g.) in dichloromethane (30 ml.), under an atmosphere of nitrogen. After one hour, the mixture was diluted with dichloromethane and washed successively with 1M hydrochloric acid, 5% w/v sodium bicarbonate solution, and saturated brine, then dried (MgSO4) and evaporated. The residue was purified by flash chromatography on silica gel (4 cm. diameter column), eluting with dichloromethane to give the title compound (0.7 g, 52%) as an oil; NMR (80 MHz, CDCl3): 1.69[m,8H, (CH2)4 ], 3.39(t,2H, OCH2CH2N), 3.90(s,3H, OCH3), 3.91 (s,3H, OCH3), 4.23(t,2H, OCH2CH2H), 4.45(s,2H, CH2.AR), 5.10(m,1H, --CHO--), 6.2(br s,1H, NHCO), 6.59-7.62(m,6H).

Workup

  1. washwashed successively with 1M hydrochloric acid, 5%
  2. dry with materialdried (MgSO4)
  3. customevaporated
  4. customThe residue was purified by flash chromatography on silica gel (4 cm. diameter column)
  5. washeluting with dichloromethane

Sources & evidence

ORD record
ord-c2801b6828ce423eaaa9fcbe4d25437d
Source dataset
uspto-grants-1989_08
Patent number
US04859692

Reaction notes

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