Formaldehyde → HCID 69322847, compound

HRID 1350162Notes

Reaction equation

HRID 1350162 reaction equation
[CH:1]([O:4][C:5]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]2[C:11]3[O:19][C@H:20]4[CH2:25][CH2:24][CH2:23][C@H:21]4[NH:22][C:10]=3[CH:9]=[CH:8][C:7]=2[N:6]=1)([CH3:3])[CH3:2].C=O.[BH3-][C:29]#N.[Na+]>C(O)(=O)C>[CH:1]([O:4][C:5]1[CH:14]=[C:13]([C:15]([F:17])([F:16])[F:18])[C:12]2[C:11]3[O:19][C@H:20]4[CH2:25][CH2:24][CH2:23][C@H:21]4[N:22]([CH3:29])[C:10]=3[CH:9]=[CH:8][C:7]=2[N:6]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69318814HCID 69318814, compound

Product 1

HCID 69322847HCID 69322847, compoundYield 97.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Compound 133 was prepared according to General Method 5 (EXAMPLE 2) from (7aR,10aS)-7,7a,8,9,10,10a-hexahydro-3-isopropoxy-1-(trifluoromethyl)-cyclopenta[5,6][1,4]oxazino[2,3-f]quinoline (5 mg, 0.014 mmol), 37% aqueous formaldehyde solution (0.01 mL, 0.14 mmol) and NaBH3CN (9 mg, 0.14 mmol) in 1 mL acetic acid to afford 5 mg of (7aR,10aS)-7,7a,8,9,10,10a-hexahydro-3-isopropoxy-7-methyl-1-(trifluoromethyl)-cyclopenta[5,6][1,4]oxazino[2,3-f]quinoline. This material (5 mg, 0.01 mmol) carried on according to General Method 4 (EXAMPLE 1) by treatment with 4 mL of 1:1 acetic acid:concentrated HCl (3 mM) heated at 90° C. for 4 h to afford 3.9 mg (90%) of Compound 133, a yellow solid, after column chromatography (3:1 hexanes:EtOAc to 1:1 hexanes:EtOAc, gradient elution). 1H NMR (500 MHz, CDCl3) δ 10.58 (bs, 1H), 7.10 (s, 1H), 7.00 (d, J=8.8, 1H), 6.87 (d, J=8.8, 1H), 4.15 (m, 1H), 3.53 (m, 1H), 2.98 (s, 3H), 2.02 (m, 4H), 1.64 (m, 2H), 0.88 (t, J=6.8, 3H).

Sources & evidence

ORD record
ord-da51ab1db66b4f61878d43ff807b7d32
Source dataset
uspto-grants-2007_05
Patent number
US07214690B2

Reaction notes

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