Chloroacetaldehyde → methyl (7R)-7-[(2-chloroethyl)(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

HRID 1669402Notes

Reaction equation

CC(O)=O.[CH:5]1([C:11]2[C:12]3[CH:13]=[CH:14][C:15]([C:32]([O:34][CH3:35])=[O:33])=[CH:16][C:17]=3[N:18]3[C:25]=2[C:24]2[CH:26]=[CH:27][CH:28]=[CH:29][C:23]=2[O:22][CH2:21][C@H:20]([NH:30][CH3:31])[CH2:19]3)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.[Cl:36][CH2:37]C=O.[BH3-][C:41]#N.[Na+]>CO>[Cl:36][CH2:37][CH2:31][N:30]([CH3:41])[C@@H:20]1[CH2:19][N:18]2[C:17]3[CH:16]=[C:15]([C:32]([O:34][CH3:35])=[O:33])[CH:14]=[CH:13][C:12]=3[C:11]([CH:5]3[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]3)=[C:25]2[C:24]2[CH:26]=[CH:27][CH:28]=[CH:29][C:23]=2[O:22][CH2:21]1

Participants

Conditions

Temperature: 60 °C

Procedure

HOAc (cat.) was added to a stirred mixture of methyl (7R)-14-cyclohexyl-7-(methylamino)-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (prepared as described in Example 1, Step 5) (0.03 M) and chloroacetaldehyde (50 wt % in water; 1.5 eq) in MeOH. NaCNBH3 (1.5 eq) was introduced and the reaction heated at 60° C. for 2 h. The reaction was allowed to cool to RT and partitioned between water and EtOAc. The organics were washed with saturated NaHCO3 (aq), brine before being dried (Na2SO4) filtered and concentrated in vacuo. The material was taken on without further purification. (ES+) m/z 480 (M+H)+; 482 (M+H)+.

Workup

temperatureto cool to RT
custompartitioned between water and EtOAc
washThe organics were washed with saturated NaHCO3 (aq), brine
dry with materialbefore being dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe material was taken on without further purification

Sources & evidence

ORD record: ord-5a201b8edb314c778f49aae4f6f4dc3c
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989438B2

Reaction notes

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